Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Pre-guideline and pre-GLP study. Only basic data given but the study is comparable to OECD TG 401.
Cross-reference
Reason / purpose for cross-reference:
reference to same study
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Study period:
No data
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
significant methodological deficiencies
Remarks:
Pre-guideline and pre-GLP study. No details on method (abraded skin or not, occlusive conditions or not). 4 animals/dose used (only 2 animals for highest dose group). Clinical signs were not observed at the two highest doses tested. Lack of coherence with respect to the rat dermal and oral data. Therefore, the study was not considered reliable for the risk assessment.
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
no details on test substance, test animals, environmental condition of animal room; 4 animals/dose used (2 animals for highest dose group); body weight, method of LD50 calculation not reported
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Remarks:
pre-GLP
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
not specified
Sex:
not specified
Details on test animals or test system and environmental conditions:
No data
Type of coverage:
not specified
Vehicle:
not specified
Details on dermal exposure:
No data
Duration of exposure:
No data
Doses:
79, 313, 1250 and 5000 mg/kg bw
No. of animals per sex per dose:
4 animals/dose (except highest dose group where 2 animals used)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Animals were observed for mortality and clinical signs daily for 14 days.
- Necropsy of survivors performed: Yes; animals that died during study and all surviving animals were subjected to gross necropsy at the end of the study period.
Statistics:
None
Preliminary study:
Not applicable
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
310 mg/kg bw
Based on:
test mat.
95% CL:
>= 160 - <= 600
Mortality:
- No mortality was observed at 79 mg/kg bw.
- 2/4, 4/4 and 2/2 animals died within 2 days post treatment at 313, 1250 and 5000 mg/kg bw, respectively
Clinical signs:
- Lethargy, slight ataxia, tachypnea, negative righting reflex, dyspnea and pupillary dilation were noted in one animal treated with 313 mg/kg bw on Day 2. Lethargy was noted in another animal from same treatment group on Day 14.
- At 79 mg/kg bw: 1/4 animals showed slight redness.
- At 313 mg/kg bw: 3/4 and 1/4 animals showed moderate and severe redness, respectively. Slight and moderate oedema was observed in 2/4 and 2/4 animals, respectively.
- At 1250 mg/kg bw: One surviving animal showed moderate redness and severe oedema (3 animals died prior to reading).
Body weight:
No data
Gross pathology:
- At 79 mg/kg bw: 3/4 animals showed red intestines areas and dark liver.
- At 313 mg/kg bw: Pale kidney, white nodules throughout the lung and red intestine areas were noted in 1/4 animals. 2/4 animals showed dark liver and lung, skin oedema and redness.
- At 1250 mg/kg bw: All animals showed mottled liver, dark lungs and skin redness. Dark spleen, kidney and liver were observed in 1/4 animals. 3/4 animals showed red intestinal areas, bloated intestine, skin oedema, brown anogenital exudate and red nose/mouth exudate.
- At 5000 mg/kg bw: Mottled liver, dark kidney, red intestinal areas, skin redness and oedema were observed in all animals. One animal showed dark lung and reduced spleen size.
Other findings:
None

None

Interpretation of results:
study cannot be used for classification
Conclusions:
The study is a pre-guideline and pre-GLP study. No details on method (abraded skin or not, occlusive conditions or not). 4 animals/dose used (only 2 animals for highest dose group). Clinical signs were not observed at the two highest doses tested. There was a lack of coherence with respect to the rat dermal and oral data. Therefore, the study was not considered reliable for the risk assessment.
Executive summary:

In an acute dermal toxicity study, groups of rabbits (4/dose except high dose where 2 animals used) were given single dermal application of test material at 79, 313, 1250 and 5000 mg/kg bw. Animals were then observed for mortality and clinical signs for 14 days and at the end of the study the surviving animals were sacrificed for macroscopic examination.

No mortality was observed at 79 mg/kg bw. 2/4, 4/4 and 2/2 animals died within 2 days post treatment at 313, 1250 and 5000 mg/kg bw, respectively. Lethargy, slight ataxia, tachypnea, negative righting reflex, dyspnea and pupillary dilation were noted in at 313 mg/kg bw. Slight skin redness was observed at 79 mg/kg bw. Slight to severe skin redness and oedema were observed in animals treated with 313 and 1250 mg/kg bw. No macroscopic abnormalities were observed in 1/4 animals at 79 and 313 mg/kg bw. At 79 mg/kg bw, gross necropsy revealed red intestines areas and dark liver in remaining animals. At 313 mg/kg bw, pale kidney, red intestine areas, white nodules in the lung, dark liver and lung, skin oedema and redness were observed. At 1250 mg/kg bw, mottled liver, dark lungs, spleen, kidney and liver, skin redness, red intestinal areas, bloated intestine, skin oedema, brown anogenital exudate and red nose/mouth exudate were observed. At 5000 mg/kg bw, mottled liver, dark kidney/lung, red intestinal areas, skin redness and oedema were observed.

 

Rabbit Dermal LD50 = 310 mg/kg bw (95 % confidence limits of 160-600 mg/kg bw)

 

Under the test conditions, the test material is classified as ‘Category 3’ according to the annex VI of the Regulation EC No. 1272/2008 (CLP).

However, the study is a pre-guideline and pre-GLP study. No details on method (abraded skin or not, occlusive conditions or not). 4 animals/dose used (only 2 animals for highest dose group). Clinical signs were not observed at the two highest doses tested. There was a lack of coherence with respect to the rat dermal and oral data. Therefore, the study was not considered reliable for the risk assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report date:
1978

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
(no details on test substance, test animals, environmental conditions of animal room and body weight. )
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Remarks:
pre-GLP
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
2-methoxy-4-propylphenol
EC Number:
220-499-0
EC Name:
2-methoxy-4-propylphenol
Cas Number:
2785-87-7
Molecular formula:
C10H14O2
IUPAC Name:
2-methoxy-4-propylphenol
Test material form:
not specified
Details on test material:
None

Test animals

Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals or test system and environmental conditions:
no data

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
not specified
Details on oral exposure:
no data
Doses:
1220, 1730, 2470 and 5000 mg/kg bw
No. of animals per sex per dose:
10 animals/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for toxicity and clinical signs daily for 14 days.
- Necropsy of survivors performed: Yes
Statistics:
None

Results and discussion

Preliminary study:
Not applicable
Effect levels
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
2 600 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 900 - <= 3 600
Mortality:
Mortality was observed in 1/10 (Day 1), 4/10 (3 animals died on Day 1; one animal died on Day 2) and 10/10 animals (Day 1) at 1730, 2470 and 5000 mg/kg bw, respectively. No mortality was observed at 1220 mg/kg bw.
Clinical signs:
Lethargy was observed in all dose groups. Also, chromodacryorrhea, ptosis and ataxia were observed at 1220, 1730 and 2470 mg/kg bw, respectively.
Body weight:
No data
Gross pathology:
- No macroscopic abnormalities were observed in 8/10, 8/10, 6/10 and 0/10 animals at 1220, 1730, 2470 and 5000 mg/kg bw, respectively.
- Necropsy of remaining animals revealed red/yellow/bloated intestines; red/bloated stomach; dark/mottled liver; kidneys - dark at 1730, 2470 and 5000 mg/kg bw; lungs dark at 2470 and 5000 mg/kg bw; yellow anogenital exudate at 2470 mg/kg bw and red nose/mouth exudate at 2470 and 5000 mg/kg bw.
Other findings:
None

Any other information on results incl. tables

Table 7.2.1.1 – Distribution of mortality

 

Observation day

Dose (mg/kg bw)

1

2

3

4

5

6

7

8

9

10

11

12

13

14

1220

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1730

1

0

0

0

0

0

0

0

0

0

0

0

0

0

2470

3

1

0

0

0

0

0

0

0

0

0

0

0

0

5000

10

0

0

0

0

0

0

0

0

0

0

0

0

0

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
Under the test conditions, test material is:
- not classified according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) as the oral LD50 is higher than 2000 mg/kg bw
- classified as category 5 according to the GHS since rat Oral LD50 is lower than 5000 mg/kg bw (2600 mg/kg bw)
Executive summary:

In an acute oral toxicity study, performed similarly to OECD Guideline No. 401, groups of rats (10 animals/dose) were administered a single oral dose of test material at 1220, 1730, 2470 and 5000 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and at the end of the study the surviving animals were sacrificed for macroscopic examination.

 

All ten animals died at 5000 mg/kg bw. 1/10 and 4/10 animals died at 1730 and 2470 mg/kg bw. No mortality was observed at 1220 mg/kg bw. Lethargy was observed in all dose groups. Also chromodacryorrhea, ptosis and ataxia were observed at 1220, 1730 and 2470 mg/kg bw, respectively. No macroscopic abnormalities were observed in 8/10, 8/10, 6/10 and 0/10 animals at 1220, 1730, 2470 and 5000 mg/kg bw, respectively. Necropsy of remaining animals revealed red/yellow/bloated intestines; red/bloated stomach; dark/mottled liver; kidneys dark at 1730, 2470 and 5000 mg/kg bw; lungs dark at 2470 and 5000 mg/kg bw; yellow anogenital exudate at 2470 mg/kg bw and red nose/mouth exudate at 2470 and 5000 mg/kg bw.

Rat Oral LD50 = 2600 mg/kg bw (95% Cl: 1900-3600 mg/kg bw).

 

Under the test conditions, test material is:

- not classified according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) as the oral LD50 is higher than 2000 mg/kg bw

- classified as category 5 according to the GHS since rat Oral LD50 is lower than 5000 mg/kg bw (2600 mg/kg bw)

This study is considered as acceptable and satisfies the requirement for acute oral toxicity