Ammonium undecafluorohexanoate

Carcinogenicity

Description of key information

Oral (OECD 453, combined chronic toxicity/carcinogenicity), rat: NOAEL neoplastic (males) = 100 mg/kg bw/day and NOAEL neoplastic (females) = 200 mg/kg bw/day

Read-across from structural analogue source substance undecafluorohexanoic acid (CAS 307-24-4).

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records

Reference

Endpoint:

carcinogenicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

Refer to analogue justification provided in IUCLID section 13

Reason / purpose for cross-reference:

read-across source

Key result

Dose descriptor:

NOAEL

Remarks:

neoplastic

Effect level:

100 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: no adverse effect observed

Remarks on result:

other: Source: CAS 307-24-4

Key result

Dose descriptor:

NOAEL

Effect level:

200 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: no adverse effect observed

Remarks on result:

other: Source: CAS 307-24-4

Key result

Critical effects observed:

no

Conclusions:

Based on the results of this study, the NOAEL for neoplastic toxicity was 100 mg/kg bw/day in male and 200 mg/kg bw/day in female rats, which was the highest dose tested.

Executive summary:

Effects on carcinogenicity/neoplastic toxicity of the target substance are estimated based on an adequate and reliable chronic oral toxicity study of a structural analogue source substance. Oral exposure of male and female rats for two years via gavage with the analogue substance caused systemic toxicity (treatment-related mortality in males and females, and systemic toxicity in females (renal effects)). There was no evidence of carcinogenicity in either male or female rats. The NOAEL for neoplastic toxicity/carcinogenicity for the analogue substance was 100 mg/kg bw/day for males and 200 mg/kg bw/day for females. Based on these results, the NOAEL for neoplastic toxicity for the target substance was 100 mg/kg bw/day for male and 200 mg/kg bw/day for female rats. As explained in the analogue justification, the differences in molecular structure between the target and the source substances are unlikely to lead to differences in neoplastic toxicity and carcinogenicity, or potency of the effects.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

100 mg/kg bw/day

Study duration:

chronic

Species:

rat

Quality of whole database:

The available information comprises adequate, reliable (Klimisch score 1) and consistent studies from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common functional groups, common breakdown products, and similarities in PC/TOX properties (refer to endpoint discussion for further details).
The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII-IX, 8.6, in accordance with Annex XI, 1.5, of Regulation (EC) No. 1907/2006.

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the read-across from a structurally similar substance, the available data on carcinogenicity/neoplastic toxicity do not meet the classification criteria according to Regulation (EC) No. 1272/2008 (CLP). The data are conclusive but not sufficient for classification.

Additional information

There is no data on carcinogenicity available for ammonium undecafluorohexanoate (CAS 21615-47-4). Thus, a read across was performed using the structurally similar substance undecafluorohexanoic acid (CAS 307-24-4). A combined chronic toxicity/carcinogenicity study was performed in male and female Sprague Dawley rats according to OECD guideline 453 and in compliance with GLP (WIL Research Laboratories, 2010). The source substance (CAS 307-24-4) was dissolved in water and administered by oral gavage at doses of 2.5, 15 and 100 mg/kg bw/day (males) and 5, 30 and 200 mg/kg bw/day (females). 60 animals per sex and dose group (70 rats for the highest dose group of each sex) were treated daily for a period of 104 weeks. A similar constituted group received the vehicle (water) and served as control.

Clinical signs of toxicity, as well as mortality and morbidity of the animals were assessed twice daily. Body weights were recorded weekly and the consumption of food was calculated. Hematological and clinical chemistry parameters were collected in study weeks 25/26 and 51/52 and urine was analysed in the same intervals. Neurobehavioral and ophthalmological examinations were included in study weeks 51 and 103, as well as gross pathological examination and histopathological analysis of all descendent and surviving animals at study termination.

Undecafluorohexanoic acid caused systemic toxicity in a dose-dependent manner and mainly affected the kidneys. Urine parameters were altered in animals of the high-dose groups and histopathological examination of the kidneys showed papillary necrosis and/or tubular degeneration in females administered 200 mg/kg bw/day. The findings were accompanied by clinical signs such as yellow material in the anogenital and the urogenital area. For additional details on systemic toxicity including clinical signs of toxicity, mortality, clinical chemistry, hematology parameters, urine analysis, gross pathological changes and non-neoplastic histopathological findings please refer to IUCLID section 7.5 on repeated dose toxicity.

There were no treatment-related neoplastic histopathological alterations observed and no evidence of carcinogenicity in either male or female rats. The incidence of neoplastic lesions in tissues and organs was similar for the control and dose groups. The NOAEL for neoplastic findings of the source substance undecaflurohexanoic acid (CAS 307-24-4) was 100 mg/kg bw/day for males and 200 mg/kg bw/day for females. Therefore, based on read-across and under the experimental conditions of the study, the target substance ammonium undecaflurohexanoate (CAS 21615-47-4) is considered to have no carcinogenic potential.