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Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Remarks:
Summary of available data used for the endpoint assessment of the target substance
Adequacy of study:
key study
Justification for type of information:
refer to analogue justification provided in IUCLID section 13
Cross-referenceopen allclose all
Reason / purpose:
read-across source
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: no information about strain used, no information on GLP, duration time not stated
Qualifier:
no guideline followed
Principles of method if other than guideline:
5 rabbits/dose, 4 doses, exposure time not mentioned, up to 14 day observation time, gross autopsy
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
no further data
Vehicle:
other: none
Details on dermal exposure:
no further data
Duration of exposure:
no data
Doses:
215, 316, 464, 681 mg/kg bw
No. of animals per sex per dose:
5 rabbits per dose
Control animals:
no
Details on study design:
no further data
Statistics:
yes, but method not mentioned
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
ca. 301 mg/kg bw
Based on:
test mat.
95% CL:
>= 213 - <= 426
Mortality:
215 mg/kg bw: 1/5; 316 mg/kg bw: 3/5; 464 mg/Kg bw: 4/5; 681 mg/kg bw: 5/5
Clinical signs:
signs of intoxication from 4 - 12 hrs post appl.: tremor, salivation sedation, recovery occurred within 3 days post application
Body weight:
initial mean body weight ranged from 2.5 - 2.7 kg; mean terminal body weight of rabbits dosed with 215 mg/kg bw: 2.3 kg (no further data given)
Gross pathology:
gross autopsy: survivors: no significant findings; decedents: inflammation of kidneys
Other findings:
dermal irritation: severe subdermal hemorrhaging, severe erythema
Interpretation of results:
other: CLP/EU GHS Category 3 (H311) according to Regulation (EC) No 1272/2008
Conclusions:
CLP: Acute tox 3, H 311
Executive summary:

To determine LD-50 value, rabbits received dermal application of 215 - 681 mg/kg bw undiluted p-cresol and were observed for sclinical signs of toxicity and mortality for up to 14 days: LD50 was determined to be 301 mg/kg bw. As signs of intoxication tremor, salivation, sedation were noted; the treated skin showed severe erythema and severe subdermal hemorrhaging.

Reason / purpose:
read-across source
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: no information about strain used, statistical evaluation not given, no guideline followed
Qualifier:
no guideline followed
Principles of method if other than guideline:
5 rabbits/dose, 4 doses, exposure time not mentioned, up to 14 days post exposure observation time
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.29 - 2.67 kg
Type of coverage:
not specified
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
no further data
Duration of exposure:
no data
Doses:
1000, 1470, 2150, 3160 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors and decedents performed: yes
- Other examinations performed: clinical signs
Statistics:
yes, method not given
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
2 050 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 590 - <= 2 650
Mortality:
1000 mg/kg bw: 0/5
1470 mg/kg bw: 0/5
2150 mg/kg bw: 4/5
3160 mg/kg bw: 4/5
Clinical signs:
signs of intoxication from 4 hrs up to 12 hrs p.a.:
lacrimation, salivation, hypersensitivity, convulsion, hypoactivity; dermal irritation: severely burned, severe oedema
Body weight:
terminal body weight: no data
Gross pathology:
survivors: no significant finding; gross necropsy-decedents: hyperemia of lungs and kidneys
Other findings:
no data

Table 1: Mortality and clinical symptoms

Dosage

mg/kg bw

onset of sympt

4-12 hrs

mortality

Mortality

cumulative

12-24 hrs

day 3

1000

0/5

1470

0/5

2150

S

4/5

4/5

3160

S

4/5

4/5

 

S = signs of intoxication from 4 hrs up to 12 hrs p.a.:

lacrimation, salivation, hypersensitivity, convulsion, hypoactivity;
dermal irritation: severely burned, severe oedema; gross necropsy-survivors: no significant finding, gross necropsy-decedents: hyperemia of lungs and kidneys

Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
CLP: not classified
Executive summary:

Application of test substance to the skin of rabbits and an exposure observation time for 14 days yielded a LD50 of 2050 mg/kg bw and severe irritational effects.

Reason / purpose:
read-across source
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dr. A. Ivanovas, Kisslegg/Allgäu/Germany
- Age at study initiation: no data
- Weight at study initiation: 210 - 235 g (male); 200 - 230 g (female)
- Fasting period before study: no
- Housing: 1 per cage
- Diet: ad libitum
- Water: ad libitum


ENVIRONMENTAL CONDITIONS
- Air-conditioned room
- Temperature (°C): 22 +- 1 °C
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Vehicle:
polyethylene glycol
Details on dermal exposure:
TEST SITE
- Area of exposure: 5 cm x 7.5 cm, shaved, intact skin
- Administration: Dosing in dissolved form by syringe (at elevated temperature to prevent precipitation)
- Type of wrap: thin aluminum foil covering the treated area and adhesive bandage ("Elastoplast") round the trunk


REMOVAL OF TEST SUBSTANCE
- Washing (if done): lukewarm water
- Time after start of exposure: 24 h


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 3 mL/kg bw of test solution (highest test volume technically achievable on the skin area)
- Concentration (if solution): 80% in PEG 300
- Constant volume or concentration used: yes
- For solid: dissolved in PEG at 50 °C, at lower temperature precipitation
Duration of exposure:
24 h

Doses:
2400 mg/kg bw (3,5-xylenol)
[Note: In report 2.4 mL/kg is mentioned, but not conclusive as 80% solution of the solid test substance in PEG should relate to w/v. 3 mL solution/kg were applied => 80% (w/v) = 2.4 g/kg bw.]
No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: several-fold on the day of treatment, thereafter daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
not applicable
Sex:
male/female
Dose descriptor:
LD0
Effect level:
2 400 mg/kg bw
Based on:
test mat.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 400 mg/kg bw
Based on:
test mat.
Mortality:
none
Clinical signs:
no particular observations
Body weight:
no significant differences from the control groups
Gross pathology:
no skin reactions (effects scores = 0) ; no particular findings at organs
Other findings:
none

No clinical signs of toxicity reported up to 2400 mg/kg

Interpretation of results:
other: CLP / GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.
Conclusions:
CLP: not classified
Reason / purpose:
read-across source
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: individual animal data not shown, no information about strain used, statistical evaluation not given, no guideline followed
Qualifier:
no guideline followed
Principles of method if other than guideline:
5 rabbits/dose, exposure period not given, observation up to 14 days, gross autopsy
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
no further data
Type of coverage:
not specified
Vehicle:
other: undiluted
Details on dermal exposure:
no further data
Duration of exposure:
no data
Doses:
681, 1000, 1470, 2150 mg/kg bw
No. of animals per sex per dose:
5 rabbits/dose
Control animals:
not specified
Details on study design:
no further data
Statistics:
yes, but method not mentioned
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
1 380 mg/kg bw
Based on:
test mat.
95% CL:
>= 841 - <= 2 260
Mortality:
681 mg/kg bw: 1/5
1000 mg/kg bw: 2/5
1470 mg/kg bw: 2/5
2150 mg/kg bw: 4/5
Clinical signs:
Hypoactivity salivation, tremors; dermal irritation: severe erythema
Body weight:
initial bw 2.44 - 2.61 kg; terminal bw not given
Gross pathology:
gross autopsy: survivors: no significant findings; decedents: hyperemia of the liver and lungs
Other findings:
no further details
Interpretation of results:
other: CLP/EU GHS Category 4 (H312) according to Regulation (EC) No 1272/2008
Conclusions:
CLP: Acute tox 4, H 312
Executive summary:

Dermal application of the testsubstance to the skin of rabbits resulted in a LD50 value of 1380 mg/kg bw (Industrial Biotest Laboratories 1969).

Data source

Materials and methods

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Effect levels
Key result
Sex:
not specified
Dose descriptor:
LD50
Remarks:
rabbit
Effect level:
ca. 301 mg/kg bw
Based on:
test mat.
95% CL:
>= 213 - <= 426
Remarks on result:
other: Source, CAS 106-44-5, p-cresol, IBTL, 1969

Any other information on results incl. tables

In the result table above the most critical value of the weight of evidence approach is given. In the following, the results are shown for the other source substances of this weight of evidence approach:

Source CAS 95 -48 -7: o-cresol: LD50 (sex unspecified, rabbit) = 1380 mg/kg bw (95% CL: >= 841 <= 2260); IBTL, 1969

Source CAS 108 -39 -4: m-cresol: LD50 (sex not specified, rabbit) > 2050 mg/kg bw; IBTL, 1969

Source CAS 108 -68 -9: 3,5-xylenols: LD50 (male/female, rat) >2400 mg/kg bw; Rütgers, 1981

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS Category 3 (H311) according to Regulation (EC) No 1272/2008
Conclusions:
Based on all available information (weight-of-evidence), following an analogue read-across approach and in the absence of data regarding acute dermal toxicity of Tar acids, Xylenol fraction (CAS 84989-06-0), Tar acids, Xylenol fraction (CAS 84989-06-0) is classified for Acute dermal toxicity (Cat. 3, H311) as a worst case.
Executive summary:

The acute dermal toxicty study on 3,5-xylenol resulted in a LD50 of > 2400 mg/kg bw for male and female rats. For the three cresol isomers the LD50 values were between 301 and 2050 mg/kg bw for rabbits. Thus, the cresol isomers seem to have a more toxic potential regarding acute dermal toxicity than 3,5-xylenol. However, as there are no acute dermal toxicity data available for Tar acids, Xylenol fraction (CAS 84989-06-0) a worst-case approach was conducted taking into account all available data on the source substances and Tar acids, Xylenol fraction (CAS 84989-06-0) was therefore classified in Cat. 3 (H311) for acute dermal toxicity according to Regulation (EC) No 1272/2008.