Amines, N-(3-aminopropyl)-N-(C16-18 and C18-unsatd. alkyl)trimethylenedi-

Carcinogenicity

Description of key information

The structurally similar N-(3-aminopropyl)-N-dodecylpropane-1,3-diamine, given via the diet daily for 104 weeks, has no carcinogenic potential in rats.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records

Reference

Endpoint:

carcinogenicity: oral

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Justification for type of information:

For details and justification of read-across please refer to the report attached in section 0.2 of IUCLID.

Dose descriptor:

NOAEL

Effect level:

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

Based on:

test mat.

Sex:

male/female

Remarks on result:

other: Effect type: toxicity (migrated information)

Dose descriptor:

LOAEL

Effect level:

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

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

other: see 'Remark'

Remarks on result:

other: Effect type: toxicity (migrated information)

Conclusions:

N-(3-aminopropyl)-N-dodecylpropane-1,3-diamine, given via the diet daily for 104 weeks, has no carcinogenic potential in rats.

Executive summary:

The test item N-(3-aminopropyl)-N-dodecylpropane-1,3-diamine was tested for carcinogenic potential in male and female rats. The animals were treated with 4 or 8 mg N-(3-aminopropyl)-N-dodecylpropane-1,3-diamine/kg b.w./day by dietary administration for 104 weeks or with 20/15/12 mg N-(3-aminopropyl)-N-dodecylpropane- 1,3-diamine/kg b.w./day by dietary administration for 61 weeks (high dosed male animals) or 81 weeks (high dosed female animals).

 

A dose-related systemic toxicity was noted. A MTD (maximum tolerated dose) as defined by the ICH guideline S1C(R2): 'Dose Selection for Carcinogenicity Studies of Pharmaceuticals' in form of e.g. no more than 10% decrease in body weight gain relative to controls, target organ toxicity and/or significant alterations in clinical pathological parameters was met by the 8 mg/kg dose level:

 

The body weight of the males and females treated with 8 mg N-(3-aminopropyl)-Ndodecylpropane-1,3-diamine/kg b.w./day was below the body weight of the control group from approximately test week 53 onwards in males (by up to 14%, statistically significant at p ≤ 0.01 in test weeks 59 to 91, 95 and 101) and from test week 75 onwards in females (by up to 12%, statistically not significant at p ≤ 0.01). In addition, changes were noted for biochemical and haematological parameters and non-neoplastic changes were noted in the heart, kidneys, skeletal muscle of the leg and larynx and mesenteric lymph nodes.

Hence, the 8 mg/kg dose was considered to be the maximum tolerated dose suitable for histopathological evaluation for neoplastic changes.

All neoplastic lesions recorded in this study were commonly encountered in rats of this strain and age. Type, incidence, and severity of the lesions recorded were not increased in the test-item treated animals as compared to the control animals.

It is concluded, that N-(3-aminopropyl)-N-dodecylpropane-1,3-diamine, given via the diet daily for 104 weeks, has no carcinogenic potential in rats.

This information is used in a read-across approach in the assessment of the target substance. For details and justification of read-across please refer to the read-across report attached to IUCLID section 0.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

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

Data for branched triamine C16-18 is based on read across from astructurally similar branched triamine C12 which was tested for carcinogenic potential in a carcinogenicity study according to OECD 453 and showed no carcinogenic potential in rats when given via the diet daily for 104 weeks.

Additional information

Data is based on read across from astructurally similar branched triamine C12. Branched triamine C16-18 only differs in the length of the alkyl chain, which issuspected to influence bioavailability, but not chemical reactivity and route of metabolisation, aspects that influence specific mechanisms of toxicity. For these reasons, many of the studies can best be performed on the substance with the shortest chain length within a group of structurally similar substances, as this is considered to result to the lowest NOAEL or most likely able to show specific effects.

N-(3-aminopropyl)-N-dodecylpropane-1,3-diamine was tested for carcinogenic potential in male and female rats. The animals were treated with 4 or 8 mg/kg b.w./day by dietary administration for 104 weeks or with 20/15/12 mg/kg b.w./day by dietary administration for 61 weeks (high dosed male animals) or 81 weeks (high dosed female animals).

A dose-related systemic toxicity was noted. A MTD was met by the 8 mg/kg dose level:

The body weight of the males and females treated with 8 mg/kg b.w./day was below the body weight of the control group from approximately test week 53 onwards in males (by up to 14%) and from test week 75 onwards in females (by up to 12%). In addition, changes were noted for biochemical and haematological parameters and non-neoplastic changes were noted in the heart, kidneys, skeletal muscle of the leg and larynx and mesenteric lymph nodes.

Hence, the 8 mg/kg dose was considered to be the maximum tolerated dose suitable for histopathological evaluation for neoplastic changes.

All neoplastic lesions recorded in this study were commonly encountered in rats of this strain and age. Type, incidence, and severity of the lesions recorded were not increased in the test-item treated animals as compared to the control animals.

It is concluded, that N-(3-aminopropyl)-N-dodecylpropane-1,3-diamine, given via the diet daily for 104 weeks, has no carcinogenic potential in rats.