Adiponitrile

Endpoint summary

Description of key information

All supporting studies were within a reasonable range of each other for all the routes of exposure.

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:

supporting study

Study period:

1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Composition of test sample known (ADN Refiner make, >99% pure). Test protocol: no reference to a test protocol, but there is a descriptin of the test. GLP: No data.

Qualifier:

no guideline available

Principles of method if other than guideline:

The test material, as a suspension in corn oil, was administered by intragastric intubation to young adult ChR-CD male rats in single dosis, one animal per dose level. survivors were sacrificed 14 days later.

GLP compliance:

not specified

Test type:

other: Acute lethal dosis

Limit test:

no

Species:

rat

Strain:

other: ChR-CD

Sex:

male

Details on test animals or test system and environmental conditions:

Young adult ChR-CD male rats.

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

None

Doses:

see table presented below

No. of animals per sex per dose:

see table presented below

Control animals:

no

Details on study design:

The test material, as a suspension in corn oil, was administered by intragastric intubation to young adult ChR-CD male rats in single dosis, one animal per dose level. survivors were sacrificed 14 days later.

Statistics:

No data

Sex:

male

Dose descriptor:

approximate LD50

Effect level:

450 mg/kg bw

Acute lethal dose 450 mg/kg rat

Interpretation of results:

moderately toxic

Remarks:

Migrated information Criteria used for interpretation of results: not specified

Conclusions:

Adiponiitrile is moderateIy toxic when administered orally to young adult: ChR-CD male rats in single doses; its Approximate Lethal Dose (ALD) is 450 mg/kg of body weight.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

215 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 20DEC1979 08FEB1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Method is described, no numerical value resulted from the testing performed. Quality issues are reported on the study.

Principles of method if other than guideline:

Five groups of five male and five female Sprague-Dawley rats per group were each exposed for six hours to different atmospheric concentrations of adiponitrile (ADN). Analytical concentrations of ADN in the chamber ranged from 0.79 to 2.18 mg/l in air.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Male and female Sprague-Dawley rats were obtained from the Charles River Breeding Laboratories. Test animals were held and observed in quarantine for seven days prior to release for the study. At the time of exposure , aninals were 42-54 days of age with males weighing 200-280 grams and females 150-202 grams. Each rat was uniquely identified by eartag and bar-coded cage card.
Animals were individually housed in suspended stainless steel wire mesh cages (23 cm x 23 cm x 21 cm) and given Purina Laboratory Standard Rodent Chow® (5001)2 and tap water (St. Louis City, MO) ad libitum except during the exposure period. Animal rooms were routinely maintained at 70-740F and 35-65% relative humidity with a 12-hour light/dark cycle.

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Duration of exposure:

6 h

Concentrations:

0.79 mg/L
1.00 mg/L
1.41 mg/L
1.56 mg/L
2.18 mg/L

No. of animals per sex per dose:

5 males and 5 females per dose.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 2.18 mg/L air (analytical)

Exp. duration:

6 h

Conclusions:

The presence of chromorhinorrhea, hemorrage of the lung and gray appearance of the lung are indications that ADN is a respiratory irritant. Only six male rats out of 50 died during the study with concentrations from 0.79 to 2.18 mg/L, making it impossible to calculate a LC50.

Executive summary:

LC50 > 2.18 mg/L. Test substance is a respiratory irritant (used for classification)

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

2 180 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Dose descriptor:

LD50

Value:

2 134 mg/kg bw

Additional information

Inhalation toxicity was difficult to determine due to difficulty getting the material in a respirable form. The key inhalation study is probably the most reliable one, but the classification was taken from the supporting study with a slightly lower LC50.

Dermal testing was stopped at 2000 mg/kg.

The oral LD 50 for male and female rats was placed at 215 milligrams per kilogram with lower and upper limits of 198 to 235 milligrams per kilogram. The compound was classed as moderately toxic by oral ingestion in male and female rats.

Justification for selection of acute toxicity – inhalation endpoint

The key study Solutia ML780341 reports a LC50 of 2900 mg/L. This result was obtained by omitting the data of the exposure to 3.7 mg/L. Therefore  the LC50 of the supporing study ML800056A was taken as a lower limit for the LD50.

Justification for classification or non-classification

DERMAL:

The only true LD50 value was from a literature search 2134 mg/kg (Drug and Chemical Toxicology. (Marcel Dekker, 270 Madison Ave., New York, NY 10016) V.1- 1977/78). An ALD (INVISTA HLR449 -75) was determined to be 2000 mg/kg and thus it can be reasonably assumed that the LD50 value is higher that the upper classification limite of 2000 mg/kg. Another study (Solutia-Y-69 -43) showed a lethal dose of > 794 mg/kg. The testing was completed on only 5 animals. After dosing of the 5th animal at 2000 mg/kg the testing was stopped. There is not enough information in this study to dispute the reliability and consistency of the other two referenced studies therefore leading to the conclusion that the LD50 is > 2000 mg/kg and therefore not classified as hazardous.

ORAL:

The classification is based on the oral LD50 for rats at 215 milligrams per kilogram with lower and upper limits of 198 to 235 milligrams per kilogram (Solutia Y-69 -43). This LD50 range is consistent with other published endpoint values (LD50 oral 155 mg/kg rat; and LD50 oral 172 mg/kg mouse - Lewis and Sax 1996). There are two studies that have lower values, however, the species used are not commonly tested species and not referenced in the CLP and the correlation between effects on humans has not been established. The acute lethal dose is above the LD50 value of 215 mg/kg and therefore the acute lethal does is not taken into account for classification.

INHALATION:

Inhalation toxicity was difficult to determine due to difficulty getting the material in a respirable form. The key inhalation study is probably the most reliable one, but the classification was taken from the supporting study with a slightly lower LC50 of 1710 mg/m3 as aerosol.