Adipic acid, compound with hexane-1,6-diamine (1:1)

Endpoint summary

Description of key information

Oral: approx. LD50 ca. 4900 mg/kg bw, (rat, BASF Test, BASF AG 1956)
Dermal: LDLo > 7940 mg/kg bw, (rat, 24 hrs, comparable to OECD 402, Younger Laboratories 1978)
The AH salt is of very low acute oral toxicity.
The acute dermal toxicity of AH-Salt is also very low.
A LC50 (inhalation toxicity) for AH salt is not available.

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:

no data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

BASF Test

GLP compliance:

no

Remarks:

pre-GLP study

Test type:

standard acute method

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Breeder
- Fasting period before study: yes
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12h/12h

Route of administration:

oral: unspecified

Vehicle:

not specified

Doses:

500, 1000, 2000, 4000, 5000, 8000, 10000 mg/kg bw

No. of animals per sex per dose:

1 or 5 animals per dose

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 8 days
- Frequency of observations: approximately 1-3 hours after dosing and then daily over a period of 8 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, gross pathology

Sex:

male/female

Dose descriptor:

approximate LD50

Effect level:

ca. 4 900 mg/kg bw

Mortality:

All but one of the animals given 5000 mg/kg bw and more died; late deaths were observed. See table below.

Clinical signs:

other: Lethal doses caused seizures. Sublethal doses led to stiff gait, apathy, reduced appetite, diarrhoea, and rough coat.

Gross pathology:

At necropsy, signs of gastro-intestinal tract irritation and intestinal bleeding were found.

Table: mortality data

Dose [mg/kg]	Mortality rate	Death occurred within
10000	1/1	3  hours
8000	5/5	1-2 days
5000	4/5	1-8 days
4000	0/5
2000	0/1
1000	0/1
500	0/1

Interpretation of results:

GHS criteria not met

Conclusions:

According to the conditions of the test, the test substance has not to be classified following EU and the GHS requirements.

Executive summary:

ALD50 was ca. 4900 mg/kg bw.

The test substance was administered via single dose gavage to groups of one or five animals per dose level. Animals were observed approximately 1-3 hours after dosing and then daily over a period of 8 days. At necropsy, all rats were examined for gross pathological changes.

All but one of the animals given 5000 mg/kg bw and more died; late deaths were observed. Lethal doses caused seizures. Sublethal doses led to stiff gait, apathy, reduced appetite, diarrhoea, and rough coat. At necropsy, signs of gastro-intestinal tract irritation and intestinal bleeding were found.

Endpoint conclusion

Dose descriptor:

LD50

Value:

4 900 mg/kg bw

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:

no data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Remarks:

This study was conducted prior to, but consistent with, US GLP guidelines published in 21 CFR 58:1978 and effective June 20, 1979.

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
2 males and 1 female New Zealand albino rabbits
Weight at study initiation: 2.3 kg (male no. 1); 2.3 kg (male no. 2); 1.9 kg (female)
No further data.

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data
- Time after start of exposure: the excess test substance was wiped off at 24 h after beginning of application

Duration of exposure:

24 h

Doses:

5010, 7940 mg/kg bw

No. of animals per sex per dose:

1 male (5010 mg/kg bw);
1 male and 1 female (7940 mg/kg bw)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: All rabbits were observed approximately 1 hour after dosing and twice daily over the 1 4-day observation period
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 7 940 mg/kg bw

Remarks on result:

other: no mortality occurred

Mortality:

No deaths occurred throughout the 14-day treatment and observation period at either dose level tested.

Clinical signs:

other: Clinical signs observed included reduced appetite and activity, salivation and ocular discharge.

Gross pathology:

At necropsy, the viscera of all animals appeared normal.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on key study data, AH-salt is not classified for dermal acute toxicity according to EU GHS classification and according to annex VI-Directive 67/548/EEC.

Executive summary:

Nylon Salt Solution (50% aqueous) was administered to the shaved, intact skin of New Zealand Albino rabbits under occlusive conditions for 24 hours. One animal was exposed to 5010 mg/kg and two rabbits were exposed to 7940 mg/kg. All rabbits were observed approximately 1 hour after dosing and twice daily over a 1 4-day observation period and given a gross necropsy. A Minimum Lethal Dose was estimated.

No deaths occurred throughout the 14-day treatment and observation period at either dose level tested. Clinical signs observed included reduced appetite and activity, salivation and ocular discharge. At necropsy, the viscera of all animals appeared normal. The dermal Minimum Lethal Dose was determined to be greater than 7,940 mg/kg in the rabbit.

Endpoint conclusion

Dose descriptor:

LD50

Value:

7 940 mg/kg bw

Additional information

ORAL

In an acute oral toxicity study (BASF 1956), groups of 1 to 5 rats were given a single dose to AH-Salt (purity not given) at doses of 500, 1000, 2000, 4000, 5000, 8000, and 10000 mg/kg bw and were observed for 8 days. Necropsy was performed at the end of the study. The oral LD50 in rats was approximately 4900 mg/kg bw.

In another acute oral study (Monsanto (1978), the minimum lethal dose was estimated. Two male and 3 female rats were given a single dose of Nylon 66 salt (50% aqueous solution) at a dose level of 10000 mg/kg bw and were observed for 14 days. Necropsy was performed at the end of the study. No mortality was caused. The viscera appeared normal.

DERMAL

In an acute dermal study (Monsanto, 1978), no deaths occurred during 24 -hour occlusive treatment and throughout the 14-day observation period at a dermal dose of 7940 mg/kg bw in two rabbits. At necropsy, the viscera of all animals appeared normal. The lowest lethal dose (LDLo) after 24 hour occlusive dermal exposure in rabbits was above 7940 mg/kg bw.

INHALATION

Studies on an acute LC50 for AH salt are not available. Such test does not need to be conducted as AH-salt vapour pressure is almost negligible.

Justification for classification or non-classification

Based on the lowest oral D50 of approximately 4900 mg/kg bw in rats, there is no need for classification according to the Directive 67/548/EC and according to EU GHS criteria (Regulation (EC) N° 1907/2006).

On the basis of the available data on acute dermal toxicity, there is no need for classification.