Amides, tall-oil fatty, N,N-di-Me

Endpoint summary

Description of key information

Older studies of acute oral and dermal toxicity are available for the submission substance.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1971

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Older proprietary study conducted prior to development of guidelines and GLP, limited information available on methods.

Qualifier:

no guideline available

Principles of method if other than guideline:

Standard acute oral toxicity study in the rat, conducted prior to development of the guidelines

GLP compliance:

no

Remarks:

study conducted prior to development of GLP

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

The animals were male and female adult albino Sprague-Dawley rats, weighing 200-300 g. They were housed in individual screen-bottom cages and provided with water and laboratory chow ad libitum.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The test substance was administered as a single dose by gavage.

Doses:

5, 10 or 20 g/kg bw

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

The animals were observed for two weeks after dosing.

Statistics:

Not applicable.

Preliminary study:

Not applicable.

Sex:

male

Dose descriptor:

LD50

Effect level:

10 000 - 20 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 1 male dosed with 5 g/kg bw died on day 3, and 1 male dosed with 10 g/kg bw died on day 3. All males dosed with 20 g/kg bw died on days 4 and 5.

Sex:

female

Dose descriptor:

LD50

Effect level:

5 000 - 10 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 1 female dosed with 5 g/kg bw died on day 3, all females dosed with 10 g/kg died between days 3 and 5, and all females dosed with 20 g/kg bw died between days 2 and 4.

Mortality:

Males: 1 male dosed with 5 g/kg bw died on day 3, and 1 male dosed with 10 g/kg bw died on day 3. All males dosed with 20 g/kg bw died on days 4 and 5.

Females: 1 female dosed with 5 g/kg bw died on day 3, all females dosed with 10 g/kg died between days 3 and 5, and all females dosed with 20 g/kg bw died between days 2 and 4.

Clinical signs:

other: Not reported.

Gross pathology:

Not reported.

Other findings:

Not reported.

Table 1. Mortality in rats following oral administration

Dose level (g/kg)	Females		Males
	No. dead/no. dosed	Day of death	No. dead/no. dosed	Day of death
5	1/6	3	16	3
10	6/6	3,5	1/6	3
20	6/6	2,4	6/6	4,5

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The estimated oral LD50 for females was between 5 and 10 g/kg bw, and for males was between 10 and 20 g/kg bw.

Executive summary:

The acute oral toxicity of DMAD (90% DMATO) was evaluated in male and female Sprague-Dawley rats. The test material was administered by gavage at dose levels of 5, 10 or 20 g/kg bw. The rats were observed for 14 days after dosing. One female and one male died at the limit dose of 5 g/kg bw. All females administered 10 or 20 g/kg bw died within 1 week of dosing. One male administered 10 g/kg bw died on day 3, and all males administered 20 g/kg bw died within 1 week of dosing. The estimated oral LD50 for females was between 5 and 10 g/kg bw, and for males was between 10 and 20 g/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

An older, guideline-comparable study is available for the submission substance and is supported by an older study in a non-standard species

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1971

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Older proprietary study, limited reporting and not comparable to current guidelines but adequate for the purposes of hazard assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

The study was conducted prior to development of the guidelines. Two rabbits per dose were evaluated for 2 weeks following a 24 hour exposure.

GLP compliance:

no

Remarks:

study conducted prior to development of GLP

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

not specified

Sex:

male

Details on test animals or test system and environmental conditions:

The animals were male adult rabbits, with body weights of 1184 to 1858 g. They were housed individually in screen-bottom cages, and supplied with water and commercial laboratory chow ad libitum.

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Test sites were clipped before exposure. The test material was injected under a rubber sleeve, fastened around the trunk of the animal. The animals were immobilised during the 24 hour exposure period. The rubber sleeve was removed after 24 hours and the rabbits returned to their cages.

Duration of exposure:

24 hours

Doses:

2, 4 and 8 mL/kg bw

No. of animals per sex per dose:

2 male rabbits/dose

Control animals:

not required

Details on study design:

The rabbits were observed for 14 days. Body weights and mortality were reported.

Statistics:

Not performed.

Preliminary study:

Not applicable.

Sex:

male

Dose descriptor:

LD50

Effect level:

8 mL/kg bw

Based on:

test mat.

Mortality:

1 rabbit exposed to 2 mL/kg bw and 1 rabbit exposed to 8 mL/kg bw died during week 1 of the observation period.

Clinical signs:

other: Not reported.

Gross pathology:

Not performed.

Other findings:

No other findings reported.

Table 1. Results.

Animal number	Dose (mL/kg bw)	Body weight (g) and mortality
		Initial	Week 1	Week 2
1	2	1560	died on test	-
2	2	1825	1823	2051
3	4	1518	1328	1662
4	4	1823	1288	1149
5	8	1858	1591	1735
6	8	1184	died on test	-

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 was reported to be 8 mL/kg bw.

Executive summary:

The acute dermal toxicity of DMAD was evaluated in six male rabbits. The study was conducted prior to development of the guidelines and GLP, has several deficiencies, but is considered to be adequate for the purposes of hazard classification. The test material was injected under a rubber sleeve fastened around the animal. Dose levels were 2, 4 and 8 mL/kg bw (2 rabbits/dose). The rubber sleeve was held in place for 24 hours, and the rabbits were observed for 2 weeks following exposure. One rabbit exposed to 2 mL/kg bw and one rabbit exposed to 8 mL/kg bw died during week 1. All surviving rabbits lost weight during week 1, and one rabbit also lost weight during week 2. The LD50 was reported to be 8 mL/kg bw. Based on a relative density of 0.891, the dermal LD50 is 7128 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Value:

7 128 mg/kg bw

Quality of whole database:

An older study is available for the submission substance. The study is not fully comparable with current guidelines but is considered to be adequate for the purposes of hazard classification. The study is supported by an older non-standard data.

Additional information

The acute oral toxicity of DMATO was evaluated in male and female Sprague-Dawley rats. The test material was administered by gavage at dose levels of 5, 10 or 20 g/kg bw. The rats were observed for 14 days after dosing. One female and one male died at the limit dose of 5 g/kg bw. All females administered 10 or 20 g/kg bw died within 1 week of dosing. One male administered 10 g/kg bw died on day 3, and all males administered 20 g/kg bw died within 1 week of dosing. The estimated oral LD50 for females was between 5 and 10 g/kg bw, and for males was between 10 and 20 g/kg bw. An acute oral LD50 of >5000 mg/kg bw is reported for the rabbit.

The acute dermal toxicity of DMATO was evaluated in six male rabbits. The study was conducted prior to development of the guidelines and GLP, has several deficiencies, but is considered to be adequate for the purposes of hazard classification. The test material was injected under a rubber sleeve fastened around the animal. Dose levels were 2, 4 and 8 mL/kg bw (2 rabbits/dose). The rubber sleeve was held in place for 24 hours, and the rabbits were observed for 2 weeks following exposure. One rabbit exposed to 2 mL/kg bw and one rabbit exposed to 8 mL/kg bw died during week 1. All surviving rabbits lost weight during week 1, and one rabbit also lost weight during week 2. The LD50 was reported to be 8 mL/kg bw. Based on a relative density of 0.891, the dermal LD50 is 7128 mg/kg bw. Other data report LD50 values of >5000 mg/kg bw in the mouse and >500 mg/kg bw in the rabbit.

The acute toxicity of the substance via the intravenous and intraperitoneal routes of exposure was investigated in the mouse and rabbit. Following intravenous administration, signs of toxicity including reduced activity, weakness, anaesthesia, laboured breathing, cyanosis, collapse, convulsions and oronasal haemorrhage were observed in the mouse and rabbit. Similar signs were seen following intraperitoneal administration but were more delayed and anaesthesia/analgesia was more prominent. Intravenous LD50 values of 300 mg/kg bw and 70 mg/kg bw are reported for the mouse and rabbit, respectively. Intraperitoneal LD50 values of 1200 mg/kg bw and >2000 mg/kg bw are reported for the mouse and rabbit, respectively.

Justification for selection of acute toxicity – oral endpoint
More reliable study in the preferred experimental species

Justification for selection of acute toxicity – dermal endpoint
More reliable study in the preferred experimental species

Justification for classification or non-classification

Classification for acute oral or acute dermal toxicity according to the Dangerous Substances Directive (67/548/EEC) or the CLP Regulation (1272/2008) is not triggered by the results of the available studies.