Document b5K0xbYvre9yYMkZj0rDGdK5o
INTEROFFICE MEMORANDUM
To____ G. B. DeLaMater
From 0. F. Eyre
cc: -C E. Blades H, E. lindenmoyer R. L. Martrich J. G. Trent
Subject
Date
22 November 1977
Ames Test of NFq
(87-0-3823)
Corporate R&D
Nitrogen trifluorida was assayed in the Ames Test and its mutagenicity
depended upon the levels of an inpurity,
As can be seen from the
data below, a 1,063 ppm 1IF3 and 5.1 ppm N2F2 exposure was mutagenic, while
a 1,046 ppm NF3 and 0.003 ppm M2F2 exposure was not mutagenic.
CF4 is not considered in this mutagenic activity because It is at the same level in both the mutagenic and nonmutagenic mixtures of HF3, and in a previous assay on 80S SF6, CF4 was at a 50 ppm level in this mixture which was not mutagenic.
Mutants Exposed To
nf3 (ppm)
2f2 (ppm)
CF4 (ppm)
8.5
106, 765 1,063k
l,046c
0.05 0.5
3.7 5.1 0.003
0.03
0.3 1.8
2.6 2.6
TA9Ba
No. Of Revertants Above Controls
+ S-9
no S-9
14 0 00
70 53 88 115
94
Mut&qenle
+ j.
-
Exposure (Hours)
94 48 48 48 48
a. Control values for TA98 in this series of assays were 24 revertants. b. Cylinder #SG13601D c. Cylinder //SG13557D
(320)
AP00049098
^ aru/ CYtctnicati-
This data implicates the impurity NgF2 as the mutagen, but NF3 is not totally exonerated since the possibility exists that NF3 and N2F2 work synergistically to produce a mutagenic effect. It would be of of interest to assay N2F2 alone. It can be concluded from these studies that NF3 at levels between 765-1',063 ppm Is mutagenic in the Amas Test provided that the impurity level of N2F2 is between 3.7-5.1 ppm. NF3 at a level of 1,046 ppm is not mutagenic in the Aires Test when N2F2 is essentially absent (0.003 ppm). Although the evidence here implicates NgFg to be a mutagen and NF3 not to be a mutagen, the absolute proof of this has not been found. Therefore, it is recomirended that the Ames Test be conducted on the following mixtures:
1. NF3 at 2,000-10,000 ppm with NgFg below 0.003 ppm. 2. NF3 at 1,000 ppm with N2F2 at 10 ppm or greater.
aee Attach
AP00049099
CHEMICAL MUTAGENICITY TEST
r
AMES PROCEDURE
CHEMICAL: REQUESTED BY
t (Afjt *
-3-
DEPARTMENT: SAMPLE:
S'^cZ'a ; > / ?*y /{
Arrived:
S' -
.a5______
7~7
Lot No.: CPC-
TEST:
Completed:
7________
Notebook Ref.; 3i;i'
Procedure: 1/499 "/Is*
RESULTS:
No. Revertants: ^7 (Xj tfav</pM Control:
No. Revertants/Nana Mole:
A//
^_______ _
Dose Response: ________________________ ___________________ ;
CONCLUSION:
A/e a/-
'< 3-1
COMMENTS:
AP00049100
ctfoi f'/uxtucCi- tW L/iCffucaCd-
*
CHEMICAL MUTAGENICITY TEST AMES PROCEDURE
r
4
CHEMICAL:
>/ ?(s
yVfJ
REQUESTED BY:
DEPARTMENT:
SAMPLE:
Arrived:
/
1
\J
sU
//. r< (
7
c. \ a )rfyf 1
?
TEST:
Completed: ? --
7
Cm* L c
* //v,~')
-
_____ Lot No.: S& /3t oa2> Notebook Ref,: 3 U L\ 3 ^ -3/ ^ 3
Procedure:
~7?fr
RESULTS:
No. Revertants: /&? fip ^
Control: _______/
No. Revertants/Nana Mole:_____________
Dose Response: ;_______________________ _____________________________ ~
CONCLUSION:
H'
COMMENTS:
y6f# f&g e * ?c ~ S -3 '
*
AP00049101
INTEROFFICE
MEMORANDUM
Subject
Date 25 July 1977
Ames Test of HFj
G. B, OelaMater____________________
_____________ .___________________________ __
(LOCiitirtil, OryAHiiotion. or Department)
m J. F. Eyre
(Locclion, o<y-:nc/at*on, or Deoarirp.erui
cc: H. E. Lindenroyer R. L. Martrich J. G.- Trent
Nitrogen tri fluoride1* was assayed in the Ames Test and was found to be
mutagenic S-9. This test indicates that NF3 is a direct acting frameshift mutagen with enzymatic activation being unnecessary. The data indicates that .the enzyme activating system (s-9) has little effect on the mutagenicity of NF^.
NF-^ ppm
8.5 ppma 106 ppmb 765 ppmb,C 1,063 ppmbjC
TA-98d
No. of Revertants Above Controls
+ S-9
no S-S
14 0
00
70 53
88 115
Mutagenic
-
+ +
a94 hour exposure. b48 hour exposure.
cTh1s mixture contained Impurities and CF4 '**- 3 ppm.
r'-6 PP'fi
^Control values for TA-98 in this series of assays was --26 revertants.
(3VU)
AP00049102
and
2- -
NF3 induced twice as many revertants as controls and displayed a dose response. Another 1250 ppm mixture of NF, with fewer impurities has been ordered by Hometown for the Amos Test.
, ban Attachment
ft J, F. 'Eyre
AP00049103
4. SAFETY CONSIDERATIONS
Enclosure t/7 27.
^==^=3"
:
"
4.3 TOXICOLOGY AND PHARMACOLOGY
4.3.3 Pharmacology
Preliminary tests have been conducted at Air Products, Inc. (61) to determine the mutagenic characteristics of NF3. The testing has involved conducting the Ames Test for Mutagenicity on NF3 of two purities and at ^riniLc rpngentrations in air. These tests have been made with and without enzyme action systems present. The results are summarized in Table 4.3-3.
Table 4.3-3 Mutagenicity of Nitrogen Trifluoride
Sample Composition, ppm
NF3 N2F2
-- 8.5
^0.005
^ 106
^0.06
^1000
M3.004
^ 760
MD.4
1063
M3. 6
Result of "Ames Test" Negative
Negative Negative Positive
Positive
\ -t.
'' A
f
The meaning of these test results is not entirely clear. They may
be interpreted differently depending upon the significance one places on the
role of the N^Fg Impurity in the NF3. The relative chemical reactivities of
Nf>F? and NF^ and the known biological effects of many N-N bonded substances
suggests that N?Fo mav have 5 ^ar greater mutagenicity than does NF3- In fact,
the results are compatible with the assumption that NF3 is non-mutagenic and
N2F2 is mutagenic at and above a concentration of 0.4 ppm. That view cannot,
however, be safely accepted based on such limited data. Ttrridre- present time,
it-is more~~prudent to -considerUMF]- as-be-lng-.-possibly mutagenic-"-at concentraXion
dtaw about
11}OQ--ppm-whe^-t-he--und44^ed^^--eontains-w&re-t-har>--6QO--and
4 -ppm of-ff^r-i'inpurl iy , 1 espeet-i-v&iyu.
(61) Private communication with Mr. Howard Lindenmo.yer, Air Products and rhnmwi r*
AP00049104
