Reaction mass of Octadec-9-en-1-yl ammonium di-n-hexyl phosphorodithioate and Octadec-9-en-1-yl ammonium mono- and di-butylphosphate

Carcinogenicity

Administrative data

Endpoint:

carcinogenicity: oral

Type of information:

other: Weight of evidence

Adequacy of study:

supporting study

Justification for type of information:

See attached weight of evidence for complete assessment.

EC 434-280-4 is a salt of an alkyl amine and one of the following three acids: an alkyl dithiodiphosphoric acid (78-64-8); mono butyl phosphate (CAS 1623-15-0); or dibutyl phosphate (DBP, CAS 107-66-4). DBP is classified as a carcinogen (category 2) and, therefore, the purpose of this assessment is to determine whether EC 434-280-4 warrants classification as a carcinogen due to the presence of DBP in the final salt reaction product. There is no residual DBP present after the reaction. In addition, the potential risk of cancer from DBP is addressed.

Based on the weight of evidence, EC 434-280-4 does not warrant classification as a carcinogen and the risk of carcinogenicity from EC 434-280-4 exposure is low.

Following are the key pieces of evidence considered to reach these conclusions:

1. DBP is classified as carcinogen based on read across from a similar material, tri-butyl phosphate (TBP, 126-73-8).
a. TBP is not a genotoxic carcinogen. The mode of carcinogenic action is by causing cellular damage in the bladder, which leads to cell proliferation and then, potentially, bladder cancer.
i. Therefore, for cancer to occur, a dose that causes urinary cell damage over extended exposure periods are required. This is based on mechanistic studies that showed the effect is reversible (does not transition to carcinoma) if exposure is stopped.
b. DBP was also negative in genotoxicity testing.
c. In a Combined Repeat Dose Toxicity Study with the Reproductive/Developmental Toxicity Screening Test (OECD 422), DBP did result in urinary bladder cell proliferation (epithelial hyperplasia), demonstrating read across from TBP is likely appropriate

2. EC 434-280-4 has a 28-day repeated dose toxicity study (OECD 407) of similar treatment length and dose (NOAEL = 30 mg/kg bw/day) to the DBP study that showed no effects on the urinary bladder
a. This is supportive evidence that the DBP associated with EC 434-280-4 is unlikely to cause urinary bladder cancer
b. It should be noted that the highest dose (300 mg/kg bw/day) was terminated after 11 days due to severe toxicity (lethality and moribundity)

3. EC 434-280-4 is currently classified as causing target organ toxicity (category 2) based on the severe toxicity that occurred, which is attributed to the alkyl amine functionality

4. Upon ingestion, it is expected that the EC 434-280-4 salt will dissociate to the starting materials, including DBP
a. The concentration of DBP required to cause bladder cell damage if EC 434-280-4 were to be ingested is unlikely to occur because other effects, characterized as severe toxicity (lethality, moribundity,) as well as immunotoxicity, will occur from EC 434-280-4 well before doses of DBP are reached that will cause bladder effects

5. EC 434-280-4 salt is stable under normal handling conditions in lubricating base oil

Materials and methods

Test material

Test material information

Constituent 1

Reference substance name:

Octadec-9-en-1-yl ammonium mono and di-butylphosphate

Molecular formula:

C22H48NO4P - C26H56NO4P

IUPAC Name:

Octadec-9-en-1-yl ammonium mono and di-butylphosphate

Constituent 2

Reference substance name:

Octadec-9-en-1-yl ammonium di-n-hexyl phosphorodithioate

Molecular formula:

C30H64NO2PS2

IUPAC Name:

Octadec-9-en-1-yl ammonium di-n-hexyl phosphorodithioate

Test material form:

liquid: viscous

Details on test material:

Material is a yellow viscous liquid