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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

8th day
p.a.

15th day
p.a.

1st-8th day
p.a.

8th-15th day
p.a.

1st-15th 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

2nd– 14thday: no clinical signs of intoxication

2

No

30 minutes: no clinical signs of intoxication

3 hours:no clinical signs of intoxication

2nd– 14thday: no clinical signs of intoxication

3

No

30 minutes: no clinical signs of intoxication

3 hours:no clinical signs of intoxication

2nd– 14thday: 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

2nd– 14thday: no clinical signs of intoxication

5

No

30 minutes: piloerection

3 hours: piloerection

2nd– 14thday: no clinical signs of intoxication

6

No

30 minutes: piloerection

3 hours: piloerection

2nd– 14thday: 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:-

2nd– 14thday: -

8

 

Humanely killed*

 

After application (approx. 2 minutes): anaemic appearance of the skin and visible mucous membranes,strong tremors, paralysis

30 minutes: -

3 hours:-

2nd– 14thday: -

9

 

Humanely killed*

 

After application (approx. 2 minutes): anaemic appearance of the skin and visible mucous membranes,strong tremors, paralysis

30 minutes: -

3 hours:-

2nd– 14thday: -

*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

2nd– 14thday: no clinical signs of intoxication

11

No

30 minutes: piloerection

3 hours: piloerection

2nd– 14thday: no clinical signs of intoxication

12

No

30 minutes: piloerection

3 hours: piloerection

2nd– 14thday: 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

Additional information

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.