2-methylhydroquinone

Endpoint summary

Description of key information

In an Acute Toxic Class Method-test according to OECD test guideline 423 the LD₅₀ (oral) of the test item, methylhydroquinone, for rats was determined to be >2000 mg/kg.

Studies regarding the acute dermal toxicity and acute inhalative toxicity do not need to be conducted because the test item, methylhydroquinone, is classified as corrosive to the skin.

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:

05.03.2018 -27.03.2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Housing: animal room with monitoring conditions – 3 animals of one sex in one plastic breeding cage
Food: maintenance pelleted diet for rats and mice - Altromin for rats/mice, Manufacturer: Altromin Spezialfutter GmbH & Co. KG, Germany ad libitum
Water: drinking water ad libitum, quality corresponding to the Regulation No. 252/2004 of Czech Coll. of Law
Microclimatic conditions: room temperature 22 ± 3 °C, permanently monitored
relative humidity 30 – 70 %, permanently monitored
light period 12-hour light/12 hour dark
Bedding: shavings of soft wood

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

The test item was administered to the stomach by tube. The single volume of administered suspension was 1 mL/100 g of animal body weight.

Doses:

The starting dose was 50 mg/kg of body weight.

No. of animals per sex per dose:

3 animals per dose

Control animals:

no

Details on study design:

Test procedure with a starting dose of 50 mg/kg was selected. This level was chosen as a starting dose because there was information about toxicity of the test item. The test item in this dose level was administered sequentially to one group of 3 females. No death of animals was observed therefore the testing was continued with higher dose 300 mg/kg (application with time distance 24 hours). Because no death of animals was observed, next step using the higher dose 2000 mg/kg was performed (application with time distance 5 days). Because this dose caused a death of one female and two females were humanely killed for moribund status, the dose level was reduced to 300 mg/kg of body weight and applied to one group of 3 females. No death of animals was observed therefore the testing was finished.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

The test item administered at the dose of 2000 mg/kg caused death of one animal and two animals were humanely killed by reason of moribund condition a few minutes after application of the test item. The clinical signs of intoxication such as anaemic appearance of the skin and visible mucous membranes, strong tremors and paralysis were observed 2 minutes after application of the test item in all three animals. During pathological examination the anaemic appearance of the skin and visible mucous membranes and the changes in the stomach as wrinkled mucosa of whitish colour were observed in all animals.

Clinical signs:

other: No serious clinical signs of intoxication were detected during whole study at the dose level 50 mg/kg (see table No. 2). At the dose level 300 mg/kg only the piloerection in all females was observed just during the first observations period (30 minutes) a

Gross pathology:

No pathologic macroscopic changes were diagnosed during pathological examination at the dose levels 50 and 300 mg/kg (see table No.6, No.7 and No.9).
During pathological examination the anaemic appearance of the skin and visible mucous membranes and the changes in the stomach as wrinkled mucosa of whitish colour were observed in all females at the dose level 2000 mg/kg (see table No.8)

Table No. 1: Individual body weight (g)

Dose   mg/kg (Step No.)	Animal No.	Body weight (g)			Body weight gain (g)
		Before application	8^th day p.a.	15^th day p.a.	1^st-8^th day p.a.	8^th-15^th day p.a.	1^st-15^th day p.a.
50 (1)	1	172.16	206.48	217.43	34.32	10.95	45.27
	2	155.71	179.26	197.44	23.55	18.18	41.73
	3	166.09	203.77	229.17	37.68	25.40	63.08
	mean	164.65	196.50	214.68	31.85	18.18	50.03
	SD	8.32	15.00	16.04	7.38	7.23	11.44
300 (2)	4	177.10	200.90	223.58	23.80	22.68	46.48
	5	178.77	211.32	233.11	32.55	21.79	54.34
	6	181.06	214.14	225.23	33.08	11.09	44.17
	mean	178.98	208.79	227.31	29.81	18.52	48.33
	SD	1.99	6.97	5.09	5.21	6.45	5.33
2000 (3)	7	200.21	-	-	-	-	-
	8	178.10	-	-	-	-	-
	9	186.15	-	-	-	-	-
	mean	188.15	-	-	-	-	-
	SD	11.19	-	-	-	-	-
300 (4)	10	163.02	192.51	208.88	29.49	16.37	45.86
	11	176.06	206.15	211.76	30.09	5.61	35.70
	12	173.18	220.37	235.55	47.19	15.18	62.37
	mean	170.75	206.34	218.73	35.59	12.39	47.98
	SD	6.85	13.93	14.64	10.05	5.90	13.46

Note:  p.a. – post application; SD – standard deviation

Table No. 2: Clinical observation – 50 mg/kg (Step No.1)

Animal No.	Death after application	Observed changes
1	No	30 minutes: no clinical signs of intoxication 3 hours:no clinical signs of intoxication 2^nd– 14^thday: no clinical signs of intoxication
2	No	30 minutes: no clinical signs of intoxication 3 hours:no clinical signs of intoxication 2^nd– 14^thday: no clinical signs of intoxication
3	No	30 minutes: no clinical signs of intoxication 3 hours:no clinical signs of intoxication 2^nd– 14^thday: no clinical signs of intoxication

 

Table No. 3: Clinical observation – 300 mg/kg (Step No.2)

Animal No.	Death after application	Observed changes
4	No	30 minutes: piloerection 3 hours: piloerection 2^nd– 14^thday: no clinical signs of intoxication
5	No	30 minutes: piloerection 3 hours: piloerection 2^nd– 14^thday: no clinical signs of intoxication
6	No	30 minutes: piloerection 3 hours: piloerection 2^nd– 14^thday: no clinical signs of intoxication

Table No. 4: Clinical observation – 2000 mg/kg (Step No.3)

Animal No.	Death after application	Observed changes
7	Yes	After application (approx. 2 minutes): anaemic appearance of the skin and visible mucous membranes,strong tremors, paralysis 30 minutes: -  3 hours:- 2^nd– 14^thday: -
8	Humanely killed*	After application (approx. 2 minutes): anaemic appearance of the skin and visible mucous membranes,strong tremors, paralysis 30 minutes: - 3 hours:- 2^nd– 14^thday: -
9	Humanely killed*	After application (approx. 2 minutes): anaemic appearance of the skin and visible mucous membranes,strong tremors, paralysis 30 minutes: - 3 hours:- 2^nd– 14^thday: -

*The females were humanely killed a few minutes after applicationby reason of moribund condition.

 

Table No. 5: Clinical observation – 300 mg/kg (Step No.4)

Animal No.	Death after application	Observed changes
10	No	30 minutes: piloerection 3 hours: piloerection 2^nd– 14^thday: no clinical signs of intoxication
11	No	30 minutes: piloerection 3 hours: piloerection 2^nd– 14^thday: no clinical signs of intoxication
12	No	30 minutes: piloerection 3 hours: piloerection 2^nd– 14^thday: no clinical signs of intoxication

Table No. 6: Pathological examination – 50 mg/kg (Step No. 1) 

Animal No.	Necropsy findings
1	Without pathologic changes
2	Without pathologic changes
3	Without pathologic changes

Table No. 7: Pathological examination – 300 mg/kg (Step No. 2) 

Animal No.	Necropsy findings
4	Without pathologic changes
5	Without pathologic changes
6	Without pathologic changes

 

Table No. 8: Pathological examination – 2000 mg/kg (Step No. 3) 

Animal No.	Necropsy findings
7	External examination: anaemicappearance of the skin and visible mucous membranes Internal examination: Stomach -  wrinkled mucosa ofwhitish colour
8	External examination: anaemicappearance of the skin and visible mucous membranes Internal examination: Stomach -  wrinkled mucosa ofwhitish colour
9	External examination: anaemicappearance of the skin and visible mucous membranes Internal examination: Stomach - wrinkled mucosa ofwhitish colour

 

Table No.9: Pathological examination – 300 mg/kg (Step No.4) 

Animal No.	Necropsy findings
10	Without pathologic changes
11	Without pathologic changes
12	Without pathologic changes

Interpretation of results:

GHS criteria not met

Conclusions:

In an Acute Toxic Class Method-test according to OECD test guideline 423 the LD50 (oral) of the test item, Methylhydroquinone, for rats was determined to be >2000 mg/kg.

Executive summary:

The test item toxicity was evaluated on the basis of mortality, clinical signs of intoxication, body weight increments during the observation period and necropsy findings at the end of study.

The test item administered at the dose of 50 and 300 mg/kg caused no death of animals. No serious clinical signs of intoxication were detected at these doses during whole study. At the dose level 300 mg/kg only the piloerection in all females was observed just during the first observations period (30 minutes) and also after 3 hours after application of the test item.

No pathologic macroscopic changes were diagnosed during pathological examination.

The test item administered at the dose of 2000 mg/kg caused death of one animal and two animals were humanely killed by reason of moribund condition a few minutes after application of the test item. The clinical signs of intoxication such as anaemic appearance of the skin and visible mucous membranes, strong tremors and paralysis were observed 2 minutes after application of the test item in all three animals. During pathological examination the anaemic appearance of the skin and visible mucous membranes and the changes in the stomach as wrinkled mucosa of whitish colour were observed in all animals.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 001 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study technically not feasible

Justification for data waiving:

the study does not need to be conducted because the substance is classified as corrosive to the skin

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study technically not feasible

Justification for data waiving:

the study does not need to be conducted because the substance is classified as corrosive to the skin

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Methylhydroquinone is not classified as acute toxic substance since the LD₅₀ (oral) for rats was determined to be >2000 mg/kg.

Studies regarding the acute dermal toxicity and acute inhalative toxicity do not need to be conducted because the test methylhydroquinone is classified as corrosive to the skin. Hence, a classification on the acute dermal and inhalative toxicity cannot be made.