trans-crotonic acid

Endpoint summary

Description of key information

Oral: LD50: 2610 mg/kg bw  for the rat 
Inhalation: no effect observed
Dermal: LD50 > 2000 mg/kg bw

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:

1967

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Remarks:

Study performed prior to implementation of GLP

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

body weight: 94-146 g

TEST ANIMALS
- Fasting period before study: yes

Route of administration:

oral: gavage

Vehicle:

other: sesame oil

Details on oral exposure:

no data

Doses:

1250; 2000; 2500; 3200; 5000 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

2 610 mg/kg bw

Mortality:

yes, after 15-210 minutes

Clinical signs:

other: decedents: show imbalance and narcosis prior to death

Interpretation of results:

GHS criteria not met

Conclusions:

The oral toxicity (LD50) of crotonic acid in female wistar rats was determined to be 2610 mg/kg bw under the test conditions.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 610 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:

supporting study

Study period:

1967

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: short summary, non GLP, no guideline followed

Qualifier:

no guideline followed

Principles of method if other than guideline:

4 h whole body exposure to an unknown air concentration of the test substance.

GLP compliance:

no

Remarks:

Study performed prior to implementation of GLP

Test type:

standard acute method

Species:

other: rats (wistar) and guinea pig

Sex:

female

Details on test animals or test system and environmental conditions:

no data

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION

- Exposure chamber volume: 28 L
- Method of conditioning air: 24.5 g of the product was vapoured at 125-130°C, Airflow: 500 liter/hour
- Temperature in air chamber: 29°C

Duration of exposure:

4 h

Concentrations:

less than 1.2 mg/L, exact concentration unknown (the evaporated test item recrystallised partly before the vapour reached the inhalation chamber)

No. of animals per sex per dose:

5 rats and 5 guinea pigs

Details on study design:

- Duration of observation period following administration: 7 days

Key result

Sex:

female

Dose descriptor:

LC0

Effect level:

> 0.9 - < 1.2 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: rats and guinea pigs were tested; actual exposure concentration unknown as the evaporated test item recrystallised partly before the vapour reached the inhalation chamber

Mortality:

no

Clinical signs:

other: no

Body weight:

no data

Gross pathology:

no data

Other findings:

no data

Based on the equation for saturated vapour concentrations it can be estimated that the concentration of the substance is approx. 0.88 mg/L saturated air at 20 °C. Therefore, it is assumed that at a temperature of 29 °C the test item concentration was between 0.88 and 1.2 mg/L.

Interpretation of results:

study cannot be used for classification

Conclusions:

Under the conditions of the present acute toxicity study the inhalation of the test item crotonic acid showed no abnormal behaviour in rats and guinea pigs.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

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:

2012-08-22 to 2012-09-19

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: DEBR 012553

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Toxi-Coop Zrt. 1103 Budapest, Cserkesz u. 90
- Age at study initiation: Young adult rats, females were nulliparous and non-pregnant
- Weight at study initiation: 274-282 g (male), 239-265 g (female)
- Housing:animals were housed individually.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 47 days (females) and 5 days (males)

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 30 - 70 %
- Air changes (per hr):8-12 air exchanges/hour by central air-condition system
- Photoperiod (hrs dark / hrs light): Artificial light, from 6 am. to 6 pm

Type of coverage:

semiocclusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: back
- % coverage: approximately 10 % of the total body surface area
- Type of wrap if used: semi-occlusive plastic wrap

REMOVAL OF TEST SUBSTANCE
- Washing:using body temperature water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount applied:The test item was uniformly applied in a single dose to at least 10 % of the total body surface area
- For solids, paste formed: yes

Duration of exposure:

24 hours

Doses:

Pretest: 5, 50, 300 and 2000 mg/kg bw dose levels, Maintest: 2000 mg/kg bw

No. of animals per sex per dose:

Pretest: 2 female animals
Maintest: 5 female and 5 male animals

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical signs: individually 1 h and 5 h after dosing, and once each day for 14 days
Body weight: shortly before treatment (pretest) and shortly before treatment, on day 7 and on day 15 (maintest)

- Other examinations performed: gross pathology

Preliminary study:

There were no deaths in preliminary study at 5, 50, 300 and 2000 mg/kg bw dose levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

no mortality

Clinical signs:

other: Neither male nor female animals treated at 2000 mg/kg bw showed behavioural changes and no systemic toxic signs were noted during the study. The test item caused dermal irritation symptoms as slight erythema, wounds and crusts that was fully reversible at

Gross pathology:

No macroscopic alterations of organs and tissues referred to the systemic toxic effect of the test item were seen during the necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the present acute dermal toxicity study with the test item Crotonic acid, the obtained acute dermal LD50 value was greater than 2000 mg/kg bw in male and female Crl:(WI)BR rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

In an acute oral toxicity study (Hoechst AG (a), 1967) female wistar rats (10 per sex and dose) were treated with Crotonic acid in sesame oil in concentrations of 1250, 2000, 2500, 3200 and 5000 mg/kg bw. Animals were found dead after 15 -210 minutes and showed clinical signs like imbalance and narcosis prior to death. Under the conditions of the study a LD50 of 2610 mg/kg bw was deduced. The study was conducted under prior to implementation of GLP and test guidelines, but follows the principles of OECD guideline 401. It is classified as reliable with restrictions.

In an acute inhalation toxicity study (Hoechst AG (b), 1967) rats and guinea pigs were exposed to vapoured Crotonic acid for 4 hours followed by a 7 day observation period. Due to the partly recrystallisation of the test item on glass vessels before the vapour reached the inhalation chamber the concentration was not applicable. No death occured and no clinical signs were observed in rats and guinea pigs under the test conditions. Due to insufficient documentation the study is classified as not assignable.

An acute dermal toxicity study (Toxi-Coop Zrt. (b), 2012) was performed with the test item Crotonic acid in Crl:(WI)BR rats, in compliance with OECD Guideline No. 402 and OPPTS 870.1200. A limit test was carried out. A single group of male and female animals (n=5 animals/sex) was exposed to Crotonic acid at 2000 mg/kg bw by dermal route. The test item was applied in its original form and left in contact with the skin for 24 hours, followed by a 14-day observation period. No mortality occurred during the study. Neither male nor female animals treated at 2000 mg/kg bw showed behavioural changes and no systemic toxic signs were noted during the study. The test item caused dermal irritation symptoms that were fully reversible within the 14 -day observation period. As no necrosis was observed and the irritation symptoms were fully reversibel Crotonic acid was considered to be slighly irritating but not corrosive after a 24h exposure period. There was no test item related effect on body weight. No macroscopic alterations of organs and tissues related to the systemic toxic effect of the test item were seen during necropsy. In this acute dermal toxicity study with the test item Crotonic acid, the obtained acute dermal LD50 value was greater than 2000 mg/kg bw in male and female Crl:(WI)BR rats.

 

Justification for selection of acute toxicity – oral endpoint
Most reliable study

Justification for selection of acute toxicity – inhalation endpoint
Most reliable study

Justification for selection of acute toxicity – dermal endpoint
Most reliable study

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on acute toxicity, the test item does not need to be classified according to Regulation (EC) No 1272/2008 (CLP), as amended for the tenth time in Regulation (EU) No 2017/776.