Document bB90YK0k8mmd9eGrk7ypdwOy3

DOW CORNING . @ TOXICOLOGICAL STUDIES CONDUCTEODN DOW CORNINGfi344 FLUID AND RELATED MATERIALS SUMMARY OF DATA BIOLOGICAL SERVICES DEPARTMENT March 9 1977 DOW CORNING CORPORATION MIDLAND MICHIGAN 48640 TELEPHONE 517 496-4000 wt ere ee ee = cee JNJTALC000479854 TOXICOLOGICAL STUDIES CONDUCTED ON DOW CORNINGfi344 FLUID AND RELATED MATERIALS SUMMARY OF DATA BIOLOGICAL SERVICES DEPARTMENT March 9 1977 JNJTALC000479855 SUMMARY OF THE TOXICOLOGICAL STUDIES CONDUCTED ON~ DOW CORNING 344 RELANAD T RELEATD ED MATERIALS Acute Oral Toxicity of a Mixture of Cyclic Polydimethylsiloxane Ten albino laboratory rats received an undiluted acute oral dose of 34.6 kg body weight No deaths or untoward effects were observed In view of the extremely large dose employed in this study it is very unlikely any significant ingestion hazard would exist from acute exposure to this fluid : oe Day Subacute Oral Toxicity Test on Dow Corning 344 Fluid A day subacute oral toxicity test was conducted on Dow Corning 344 fluid Physiological saline was used as a treated control material | No adverse findings were noted in the parameters investigated such as mortality behavioral reactions body weights gross pathologic studies and seminal vesicle weights and ratios cS a . Acute Aerosol Inhalation Toxicity of Dow Corning 344 Fluid Albino rats were exposed to Dow Corning 344 fluid for a period of 7-1 hours The aerosol concentration was approximately 90 liter The exposure consisted of an aerosol burst every 1/2 hour for a total _ of 15 exposures over the 7-1 hour period Based on the parameters investigated such as body weight mortality behavioral reactions and gross pathologic examination acute aerosol exposure to Dow Corning 344 fluid appears to present no apparent hazard Day Subacute Aerosol Inhalation Toxicity of Dow Corning 344 Fluid A day subacute aerosol inhalation toxicity study was conducted with 997 using cynomolgus monkeys as experimental animals 1015 was used as treated control material Twelve monkeys were divided equally into two groups designated treated control T T was exposed to the aerosol of Dow Corning 344 fluid and the treated control animals were exposed to the propellent Each inhalation chamber 3.5 cubic meter Plexiglasfi received clean air from the top center of the chamber at a rate of 25 min Each group was exposed to its respective aerosol twice daily each exposure consisting of four second sprays with five minute intervals between sprays for 90 consecutive days The average set of four aerosol releases from the treated control and T were 73.9 and 78.9 grams respectively The average daily nominal concentrations _ were 147.2 and 158.3 mg air for treated control and T respectively Filter samples taken daily from the T chamber revealed an average analytical concentration of 0.005 mg air JNJTALC000479856 During the course of the study animals were observed and data with respect to incidence of mortality food consumption reactions displayed body weight hematologic and clinical blood chemistry profiles urinalyses opthalmic examinations respiratory function tests and neurological examinatiowenrse collected All numerical data from the test group were compared to the treated control group when statistically possible by tests On day 91 of the investiga- tion all animals were given complete gross and microscopic pathologic | examination : No deaths occurred during the experiment and no untoward behavioral reactions were observed Growth as indicated by body weight data was unaffected by exposure to the test compounds No changes in food or water consumption patterns of the animals were observed during the testing program Opthalmic examinations following the exposure periods revealed no treatment ocular lesions confirmed histologically Neurological examinations including evaluation of the righting supporting flexor extensor thrust and patelloar knee jerk reflexes revealendo differences between test and control monkeys Ten lead electrocardiograms conducted during the study revealed no ' abnormalities in. Hematologic studies including total and differential leukocyte counts erythrocyte counts hemoglobin concentration hematocrit sedimentation rate and calculated cell indices revealed no differences between test and control monkeys Clinical blood chemistry studies including fasted blood glucose concentration blood urea nitrogen concentration serum alkaline phosphatase activity serum glutamic transaminase activity were unremarkable Urinalyses which included determinations for the presence of blood ketones glucose reducing substances proteins and microscopic formed elements showed no treatment abnormalities Respiratory function studies including air way resistance dynamic compliance respiratory rate average tidal volume minute volume PC02 pH functional residual capacity lung clearance index fraction of CO2 removed from respired air diffusing capacity of CO2 and of 02 peak flow and total plural pressure failed to reveal any treatmentrelated changes No differences between test and control monkeys were apparent following gross pathologic examination and evaluation of organ weight data Histopathologic studies revealed no lesions which could be attributed to inhalation of the test material The Results of Range Finding Toxicological Tests on Octamethylcyclotetrasiloxane Octamethylcyclotetrasiloxane has a low acute oral toxicity ALD is 2 kg It is very slightly irritating to the eye and causes essentially no irritation to the skin upon prolonged contact The vapor of this material at room temperature or when generated at 100 is without appreciable effects upon laboratory animals JNJTALC000479857 Chronic Eight Month Feeding Studies with Various Methylsiloxanes in Rabbitso j The effects of dietary administration to rabbits of a series of polymerized methylsiloxanes have been studied by a number of parameters of physiological status and tissue morphology No significant differences were noted on hemograms leukocytic data blood chemical data urine " analytical findings organ weights and gross or microscopic appearances of tissue from all organ systems among the groups A scattered incidence of unusual findings seen throughout all groups were attributed to the - . type of respiratory infection or parasitic infestations often seen in comparable colonies of control animals of this species It was concluded that ingestion of 0.05 of a 1-5 mixture of the trimer and tetramer of % of the cyclic trimer or tetramer or trimethyl endblocked DOW CORNINGfi200 fluid 1.5 cs by rabbits for eight months produced no significant adverse effects Chronic Year Feeding Studies with Methylsiloxane Fluids in Rats A study comparinthge effects of dietary administration to rats of 0.05 of a 1-5 mixture of dimethylcyclictrimer and dimethylcyclictetramer % _ dimethylcyclictrimer % dimethylcyclictetramer or % trimethyl end- blocked Dow Corning 200 fluid 5 cs with those of an unsupplemented diet was conducted Over a one year period no significant differences were - noted in growth or in the physiological status of the rats receiving any control of these methylsiloxanes in comparison to the base of the group Post mortem examinations showed no treatment differences in organ weights or gross and microscopic appearance of tissues It was concluded that administration of methylsiloxanes in the diet of rats for more than one year did not have any adverse effects Human Repeated Insult Patch Test HRIPT Dow Corning 344 fluid failed to produce any evidence of primary irritation or skin sensitization following nine daily repeated applications to each of fifty human subjects skin A Publication Entitled Toxicological Studies on Certain Commercial Silicones by Rowe Spencer and Bass This publication deals with single dose oral administration repeated dose oral administration intraperitoneal injection subcutaneous injection eye installation skin application single exposure vapor inhalation and repeated exposure vapor inhalation In conclusion these toxicological studies with laboratory animals have shown the subject methyl silicones ranging in viscosity from 0.65 centistoke to 12,500 centistokes to respond ina similar manner and to be low in toxicity and most likely present no significant handling problems JNJTALC000479858 10 A Publication Entitled Health and Environmental Aspects of Polydimethylsiloxane Fluids by Calandra Keplinger Hobbs and Tyler The reprint gives details on the acute subacute and chronic oral ingestion toxicity effects upon injection skin and eye response acute and subacute inhalation studies reproductive teratologic and mutagenic response Environmental studies including the effectosn various birds aquatic and marine species and biodegradation and bioaccumulation are detailed linear Human and animal metabolism of various cyclic and siloxanes also outlined polydimethyl- polydimethyl- Dow Corning Internal Company Report No. 1723-2 2Dow Corning Internal Company Report No. 1547-80A Dow Corning Internal Company Report 1547-1 an Dow Dow Corning Internal Company Report No. 2061-1 5 Dow Corning 6 Dow Corning 7 Dow Corning Internal Internal Internal Company Report No. Company Report No. Company Report No. 1362-1 1179-1 1179-1 8 Dow Corning Internal Company Report No. 2061-1 fh JNJTALC000479859