4,4'-carbonimidoylbis[N,N-diethylaniline] monohydrochloride

Carcinogenicity

Description of key information

Non carcinogenic NOAEL was considered to be 100 mg/kg bw when Albino male and female rats were treated with 4,4'-carbonimidoylbis(N,N-diethylaniline) hydrochloride orally in feed for 20-21 months.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records

Reference

Endpoint:

carcinogenicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

Data is from study report

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 451 (Carcinogenicity Studies)

Principles of method if other than guideline:

Carcinogenicity Study of Calcozine Yellow SFW Unblended In Albino Rats

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material (as cited in study report): Calcozine Yellow SFW Unblended (4,4'-carbonimidoylbis(N,N-diethylaniline) hydrochloride)
- Molecular formula (if other than submission substance): C21-H29-N3.Cl-H
- Molecular weight (if other than submission substance): 359.942 g/mole
- Substance type: Organic
- Physical state: No data available
- Purity: No data available
- Impurities (identity and concentrations): No data available

Species:

rat

Strain:

not specified

Remarks:

Albino

Details on species / strain selection:

No data available

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data available

Route of administration:

oral: feed

Type of inhalation exposure (if applicable):

not specified

Vehicle:

not specified

Remarks:

Feed

Remarks on MMAD:

No data available

Details on exposure:

Calcozine Yellow SFW Unblended feed to albino rats at a dIetary level of 0.1%

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

20-21 months

Frequency of treatment:

Daily

Post exposure period:

No data available

Remarks:

0 and 100.0 mg/kg bw/day

No. of animals per sex per dose:

No data available

Control animals:

yes, concurrent vehicle

Details on study design:

No data available

Positive control:

Auramine is used as positive control.

Observations and examinations performed and frequency:

Survival and body weight were observed.

Sacrifice and pathology:

Gross pathology and histopathology were examined.

Other examinations:

No data available

Statistics:

No data available

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality:

mortality observed, non-treatment-related

Body weight and weight changes:

effects observed, non-treatment-related

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

effects observed, non-treatment-related

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

effects observed, non-treatment-related

Histopathological findings: neoplastic:

effects observed, treatment-related

Other effects:

not specified

Details on results:

Mortality: No effect on survival of treated rats was observed as compared to control.

Body weight and weight gain: A less marked reduction in body weight gain was observed as compared to positive control.

Gross Pathology: 25 % (7/28) Nodules were observed on the livers of treated male and female rats as compared to 59% (20/34) positive control and No unusual growth was observed in the control rat livers.

Histopathology: non-neoplastic: Primary lesion of focal to diffuse hyplerplastia of the liver cells were observed in treated rats as compared to control but not significant as compared to positive control.
Minor focal lesions of degeneration, necrosis, fatty metamorphosis, inflammation, bile duct proliferation and cholangiofibrosis were observed in the liver of control, positive control and treated animals. However, the severity of these lesions was generally grater in the livers of the positive control animals than in the Iivers of control or treated animals.

Histopathology: neoplastic: Hepatomas were present in 2/9 male and 1/19 female that survived the length of the investigation. There were no hepatomas observed in any of the treated animals that died prior to the conclusion of the study. However, there were no hepatomas observed in any of the test animals that died prior to the conclusion of the investigation.

Dose descriptor:

NOAEL

Effect level:

100 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No effect on survival, body weight, gross pathology and histopathology

Critical effects observed:

not specified

Conclusions:

Non carcinogenic NOAEL was considered to be 100 mg/kg bw when Albino male and female rats were treated with 4,4'-carbonimidoylbis(N,N-diethylaniline) hydrochloride orally in feed for 20-21 months.

Executive summary:

In a Carcinogenicity study, Albino male and female rats were treated with 4,4'-carbonimidoylbis(N,N-diethylaniline) hydrochloride in the concentration of 100 mg/kg bw orally in feed. No effect on survival of treated rats was observed as compared to control. A less marked reduction in body weight gain was observed in treated male and female rats as compared to positive control. Similarly, 25 % (7/28) Nodules were observed on the livers of treated male and female rats as compared to 59% (20/34) positive control and No unusual growth was observed in the control rat livers. Primary lesions of focal to diffuse hyplerplastia of the liver cells were observed in treated rats as compared to control but not significant as compared to positive control. Minor focal lesions of degeneration, necrosis, fatty metamorphosis, inflammation, bile duct proliferation and cholangiofibrosis were observed in the liver of control, positive control and treated animals. However, the severity of these lesions was generally grater in the livers of the positive control animals than in the Livers of control or treated animals. In addition, Hepatomas were present in 2/9 male and 1/19 female that survived the length of the investigation. There were no hepatomas observed in any of the treated animals that died prior to the conclusion of the study. However, there were no hepatomas observed in any of the test animals that died prior to the conclusion of the study. But, as compared to positive control (17/23 male and 9/11 female), the number of Hepatomas are less. Therefore, non carcinogenic NOAEL was considered to be 100 mg/kg bw when Albino male and female rats were treated with 4,4'-carbonimidoylbis(N,N-diethylaniline) hydrochloride orally in feed for 20-21 months.

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:

Data is Klimisch 4 and from study report

System:

other: Not spcified

Organ:

not specified

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 above study on 4,4'-carbonimidoylbis(N,N-diethylaniline) hydrochloride, it can be concluded that NOAEL value is 100 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 4-methylphenyl acetate can be “Not classified” for Carcinogenic toxicity.

Additional information

Carcinogenicity- Oral:

In a study,4,4'-carbonimidoylbis(N,N-diethylaniline) hydrochloride(CAS no 6358-36-7) has been investigated for Carcinogenic toxicity to a greater or lesser extent. Study based on in vivo experiment data in rodents, i.e. most commonly in rat for 4,4'-carbonimidoylbis(N,N-diethylaniline) hydrochloride.

In NTRL study report OTS0539600; B 8723; 1992, Carcinogenicity was evaluated in Albino male and female rats by using 4,4'-carbonimidoylbis(N,N-diethylaniline) hydrochloride in the concentration of 100 mg/kg bw orally in feed. No effect on survival of treated rats was observed as compared to control. A less marked reduction in body weight gain was observed in treated male and female rats as compared to positive control. Similarly, 25 % (7/28) Nodules were observed on the livers of treated male and female rats as compared to positive control 59% (20/34) and No unusual growth was observed in the control rat livers. Primary lesions of focal to diffuse hyplerplastia of the liver cells were observed in treated rats as compared to control but not significant as compared to positive control. Minor focal lesions of degeneration, necrosis, fatty metamorphosis, inflammation, bile duct proliferation and cholangiofibrosis were observed in the liver of control, positive control and treated animals. However, the severity of these lesions was generally grater in the livers of the positive control animals than in the Livers of control or treated animals. In addition, Hepatomas were present in 2/9 male and 1/19 female that survived the length of the investigation. There were no hepatomas observed in any of the treated animals that died prior to the conclusion of the study. However, there were no hepatomas observed in any of the test animals that died prior to the conclusion of the study. But, as compared to positive control (17/23 male and 9/11 female), the number of Hepatomas are less. Therefore, non carcinogenic NOAEL was considered to be 100 mg/kg bw when Albino male and female rats were treated with 4,4'-carbonimidoylbis(N,N-diethylaniline) hydrochloride orally in feed for 20-21 months.

Thus, based on the above study on 4,4'-carbonimidoylbis(N,N-diethylaniline) hydrochloride, it can be concluded that NOAEL value is 100 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 4-methylphenyl acetate can be “Not classified” for Carcinogenic toxicity.