Pyrazole

Endpoint summary

Description of key information

Oral: rat LD50: 1010 mg/kg bw. Reliability = 2

Dermal: rabbit LD50: 400 mg/kg. Standardized test protocol. Reliability = 2

Inhalation: rat 4 -hour LC50: >0.37 mg/L (maximum attainable concentration). OECD 403. Reliability = 1

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Remarks:

Acceptable, well documented publication/ study report which meets basic scientific principles.

Principles of method if other than guideline:

The LD50 was determined after a 24-hour fast with free access to tap-water.

GLP compliance:

not specified

Test type:

standard acute method

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 205-220 g
- Housing: each housed in individual cages
- Diet: commercial standard solid diet (Altromin-R) ad libitum
- Water: ad libitum

Route of administration:

oral: unspecified

Doses:

840-1214 mg/kg

No. of animals per sex per dose:

2 groups of 40 rats each

Control animals:

not specified

Details on study design:

The LD50 was determined after a 24-hour fast with free access to tap-water.

Sex:

not specified

Dose descriptor:

LD50

Effect level:

1 010 mg/kg bw

The minimal lethal dose was 850 mg/kg. After single doses larger than 1000 mg/kg leading to a comatose state with death occurring within 12 -36 h, no liver cell alterations were seen microscopically; livers of rats dying 6 -11 days after 850 -1000 mg/kg showed extensive centrolobular necrosis with inflammatory reactions and appearance of fat ill surviving liver cells.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

LD50 (rat): 1010 mg/kg

Executive summary:

The oral LD50 of the test substance was determined after a 24-hour fast with free access to tap-water. The minimal lethal dose was 850 mg/kg. Single doses larger than 1000 mg/kg lead to a comatose state with death occurring within 12 -36 hours with no liver cell alterations observed microscopically. Liver effects were observed in rats dying 6 -11 days after 850 -1000 mg/kg. The LD50 was 1010 mg/kg.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 010 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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

strain: SPF Wistar/Chbb : THOM ; breeding facility: Dr. K . Thomae GmbH, D-7950 Biberach, FRG)
Mean body weight at the beginning of the study: male animals 285 ± 4.0 g, female animals 188 ± 2 .1 g.
Age at the beginning of the study: approx . 8- 9 weeks
The animals were identified by color marking on the tail.
The animals were offered KLIBA rat/mouse laboratory diet 24-343-4 10 mm pellets, Klingentalmuhle AG, CH-4303 Kaiseraugst, Switzerland, and drinking water ad libitum during the post-exposure observation period.
The animals were kept in fully air-conditioned rooms in which a temperature in the range 20-24°C and relative humidity in the range 30-70% were regulated by means of a central air-conditioning system.

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

0.37 mg/L

No. of animals per sex per dose:

5

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 0.37 mg/L air

Remarks on result:

other: maximum concentration achievable

Mortality:

No mortality was observed during the study.

Clinical signs:

other: Clinical signs included wiping of snouts, restlessness, and attempts to escape. All animals were clear of findings by 2 hours after the beginning of exposure.

Body weight:

The body weight gain of male rats was not affected. The body weight gain of the female rats was retarded in the second week of the observation period.

Gross pathology:

No pathologic findings noted.

Cumulated lethality on day	male	female
0	0/5	0/5
1	0/5	0/5
2	0/5	0/5
7	0/5	0/5
14	0/5	0/5
Total at end of the study	0/5	0/5

Time after beginning of exposure	< ¼ h	¼ h	½ h	1 h	2 h	3 h	4 h
Animals without findings					10	10	10
Wiping of snouts		10
Restlessness		10	10	10
Attempts to escape	10

 

Interpretation of results:

GHS criteria not met

Conclusions:

Regarding the results of the study, the LC50 of the test substance exceeds the maximum concentration that could be technically achieved (0.37 mg/L air).

Executive summary:

The acute inhalation toxicity potential of the test substance was studied in accordance with OECD Guideline 403. Five male and five female rats were exposed to the test substance for 4 hours at a concentration of 0.37 mg/L (maximum attainable concentration). No mortality or gross pathologic findings were noted was observed.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Qualifier:

no guideline followed

Principles of method if other than guideline:

Standardized test (BASF-Test) to assess the acute dermal toxicity in rabbits.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

Vienna White

Sex:

male/female

Details on test animals or test system and environmental conditions:

Breeder: GAUKLER, 6050 Offenbach
Mean weight for - males: 3.0 kg - females: 3.0 kg
The animals had Ssniff K, standard laboratory diet for rabbits and guinea pigs, INTERMAST GMBH, Soest and water ad libitum.

Type of coverage:

occlusive

Vehicle:

water

Duration of exposure:

24 h

Doses:

200 and 400 mg/kg (50% in water)

No. of animals per sex per dose:

3

Control animals:

no

Sex:

male/female

Dose descriptor:

LD50

Effect level:

400 mg/kg bw

Mortality:

see table below

Clinical signs:

other: Apathy, diarrhoea

Gross pathology:

Dead animals: acute dilatation of the heart (right), degeneration; loamy liver with acute dystrophy; sandy kidneys with nephrosis
Killed animals: no substance-related pathological findings

Mortality

Dose mg/kg	Conc. %	Animal	1 h	24 h	48 h	7 days	14 days
400 200	50 50	3 m 3 f 3 m 3 f	0/3 0/3 0/3 0/3	0/3 0/3 0/3 0/3	0/3 0/3 0/3 0/3	1/3 2/3 0/3 0/3	1/3 2/3

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

LD50 (rabbit): 400 mg/kg

Executive summary:

A standardized test (BASF-Test) to assess the acute dermal toxicity in rabbits was performed. Three male and female rabbits per dose were exposed to the test substance under occlusive conditions for 24 hours to doses of 200 and 400 mg/kg (50% in water). The dermal LD50 in rabbits was 400 mg/kg.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

400 mg/kg bw

Additional information

In a study using the standard acute method, several dose levels between 840 and 1214 mg/kg bw of the test substance (purity unknown) were administered once orally to groups of 40 rats. The LD50 was 1010 mg/kg bw. The minimal lethal dose was 850 mg/kg bw. After single doses larger than 1000 mg/kg bw leading to a comatose state with death occurring within 12 -36 h, no liver cell alterations were seen microscopically; livers of rats dying 6 -11 days after 850 -1000 mg/kg bw showed extensive centrolobular necrosis with inflammatory reactions and appearance of fat ill surviving liver cells.

In a limit test according to OECD Guideline 403, five male and female Wistar rats were whole-body exposed for 4 hours to a dynamically produced vapour with an analytical concentration of 0.37 mg/L (purity 100%). This concentration is the maximum concentration that could be achieved technically. There were no mortalities and no necropsy findings observed. Clinical signs (wiping of snouts, restlessness and attempts to escape) were only observed during exposure. The body weight gain of the males was not affected while the body weight gain of the females was retarded in the second week of the observation period. The LC50 of this study is > 0.37 mg/L.

Following a standardized test protocol (BASF test), groups of three male and three female Vienna White rabbits were treated for 24 hours with doses of 200 mg/kg bw or 400 mg/kg bw of the test substance (purity unknown, prepared in 50% water) epicutaneously under occlusive conditions. Three of six animals died in the high dose treatment and 0/6 in the low dose treatment, leading to a LD50 of 400 mg/kg bw. Clinical signs were apathy and diarrhoea. At necropsy, acute dilatation of the heart (right), degeneration, loamy liver with acute dystrophy and sandy kidneys with nephrosis were observed in animals that died; sacrificed animals were found without substance-related findings.

Justification for classification or non-classification

Based on an oral LD50 in rats of 1010 mg/kg, the test substance is classified for acute oral toxicity as Cat 4 (H302: Harmful if swallowed) according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

 

Based on a dermal LD50 in rabbits of 400 mg/kg, the test substance is classified for acute dermal toxicity as Cat 3 (H311: Toxic in contact with skin) according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

 

Based on a 4-hour inhalation LC50 in rats of >0.37 mg/L (highest attainable concentration) the test substance is not classified for acute inhalation toxicity according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.