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Description of key information

LD50 oral (rat): 300 mg/kg
LC0 inhalation (8h)(rat) > 2.8 mg/L
LD50 dermal (rat): 600 mg/kg

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:
other: The purity of the test substance and the strain of rat used are not known. The administration volume and the use of vehicle are not specified.
Qualifier:
equivalent or similar to guideline
Guideline:
other: Federal register (see below)
Deviations:
not specified
Principles of method if other than guideline:
Federal Register (1961) pp. 7333-7341, Part 191- Hazardous Substances: Definitions and Procedural and Interpretative Regulations, Final Order
GLP compliance:
no
Test type:
other:
Limit test:
no
Species:
rat
Strain:
other: albino
Sex:
male
Details on test animals or test system and environmental conditions:
no data
Route of administration:
oral: gavage
Vehicle:
not specified
Doses:
158, 316, 630 and 1260 mg/kg bw
No. of animals per sex per dose:
5 males per dose
Control animals:
yes
Details on study design:
- Rats were observed during a 14-day post-exposure period.
Sex:
male
Dose descriptor:
LD50
Effect level:
300 mg/kg bw
95% CL:
200 - 500
Mortality:
0/5 rat died at the dose of 158 mg/kg bw.
2/5 rats died at the dose of 316 mg/kg bw on day 1 and 2.
5/5 rats died at the dose of 630 mg/kg bw by day 1.
5/5 rats died at the dose of 1260 mg/kg bw within 1 hour.
Clinical signs:
no data
Body weight:
Except one of the surviving rats, all showed body weight gains increase within significant limits of those of control animals.
Gross pathology:
None of the rats sacrificed following the holding period exhibited any gross lesions upon pathological examination.
Other findings:
The rats that died during the observation period revealed hyperaemia of the stomach and intestine.
Interpretation of results:
Category 3 based on GHS criteria
Conclusions:

Based on this study, Catechol is classified as Acute. Tox. Category 3, H301 according to EU GHS Regulation.
Executive summary:

In an acute oral toxicity study (Flickinger, 1967), groups of 5 albino male rats were given a single oral dose of catechol at doses of 0, 158, 316, 630 and 1260 mg/kg bw and observed for 14 days.

No death occured at 158 mg/kg bw, 2/5 died at 316 mg/kg bw and 5/5 at 630 mg/kg bw.

No clinical signs were reported and the autopsy revealed for rats died during the study: hyperemia of the stomach and intestines. None of the rats sacrifed at the end of the experiment revealed gross pathology during pathological examination.

 

Oral LD50Males = 300 mg/kg bw (95% C.L. 200-500 mg/kg)

Catechol is considered to be toxic if swallowed based on the LD50 obtained.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
300 mg/kg bw
Quality of whole database:
The study is coated with reliability 2.

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Only 6 female rats were tested instead of 5 males and 5 female rats. Purity is unspecified.
Qualifier:
equivalent or similar to guideline
Guideline:
other: Federal register (see below)
Deviations:
not specified
Principles of method if other than guideline:
Federal Register (1961) pp.7333-7341, Part 191- Hazardous Substances: Definitions and Procedural and Interpretative Regulations, Final Order
GLP compliance:
no
Test type:
other: inhalation study
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan, no more data
- Age at study initiation: no data
- Weight at study initiation: 87 to 126 grams
No more data
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
not specified
Vehicle:
other:
Details on inhalation exposure:
- Aerosol generation system: 
Samples were dissolved in distilled water and the resulting solutions were aerosolised using a D18 Dautrebande aerosol generator operated at 30 psi. At this operating pressure, the D18 generator delivers droplet diameters of 1 µ size and smaller. Airborne concentrations were determined by measurement of the volume loss of solution following aerosolisation. 
The weight of sample present in that volume was then calculated and related to the total volume of air used in generating the aerosol to obtain chamber concentrations. The nominal airborne concentrations of sample were 1500, 2000 and 2800 mg/m3.
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
8 h
Concentrations:
1.5, 2.0 and 2.8 mg/l (nominal)
No. of animals per sex per dose:
6 females per dose
Control animals:
not specified
Details on study design:
Animals were held for 14 days following exposure and were then weighed and sacrificed for gross necropsy.
Rats were observed during a 14-day post-exposure period.
Sex:
female
Dose descriptor:
LC0
Effect level:
>= 2.8 mg/L air
Exp. duration:
8 h
Mortality:
No deaths resulted when rats inhaled catechol-water aerosols at 1500, 2000 and 2800 mg/m3. 
Clinical signs:
other: Signs of intoxication are irritation, persisting tremors 24H after exposition. No effects were observed at 1.50 mg/l.
Body weight:
All animals had normal 14-d weight gain
Gross pathology:
No lesion attributable to inhalation of aerosol was seen at gross necropsy. 
Other findings:
Prior to sacrifice at the conclusion of the 14-day holding period, all six rats previously subjected to an aerosol of 2.8 mg/l had blackened toes and tails. Some of the toes of several of these rats were missing, as well as the tips (2 cm and less) of the tails of all six rats. 
Similar tail loss occurred in 2/6 rats subjected to 2.0 mg/l aerosol, while none of the 6 had this condition 14 d after inhaling an aerosol of 1.5 mg/l. The loss of distal portions of the tail and accompanying loss of digits at doses of 2.8 and 2.0 mg/l was dose related. This loss of appendages by absorption of various amount of catechol (including lethal doses) through the intact skin and gastroenteric tract of various animals has not been noted in the literature.
Other toxic signs were reported: tremors within 6 or 7 hours and persisted trough first post-exposure day, and normal in the second post-exposure day.
Interpretation of results:
GHS criteria not met
Conclusions:
Since no mortality was observed at the higher tested concentration (2.8 mg/L) Catechol is not classified harmful by inhalation route.
Executive summary:

In a study (Flickinger, 1976), 6 female Wistar rats were exposed to aerolizated solutions of catechol at nominal doses from 1.5, 2 and 2.8 mg/L for 8 hours. The LC0 (8h) was > 2.8 mg/L. At this dose, no mortality occured, but effects were noted on central nervous system and loss of tail and toes.

Based on the LC0 and according to CLP Regulation criteria, catechol is not considered as harmful by inhalation route.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The study was coated with reliability 2. No mortality was observed at the higher tested dose (2.8 mg/L).

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:
other: The LD50 was calculated but the calcul method used is not explained.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
not specified
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals or test system and environmental conditions:
No data
Type of coverage:
open
Vehicle:
other: distilled water
Duration of exposure:
24 hours
Doses:
125, 875, 1125 mg/kg b.w.
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- 2,5 ml/kg of the substance solution was placed and carefully spread out over a beforehand shaven cutaneous zone of the area of the back (surface  of approximately 4 X 7 cm; which corresponds to a little less than 10% of total body surface).
- animals were placed after treatment in individual cages and they are fitted with a collar to prevent that they do not lick.
- 24 hours after treatment, the surviving animals were released from their collar and the zone of application was carefully washed with warm soapy water, then dried.
- Animals were observed during 15 days after treatment.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
600 mg/kg bw
Mortality:
0/10 at 125 mg/kg.
10/10 at 875 and 1125 mg/kg.
Clinical signs:
At 125 mg/kg: none.
At 875 and 1125 mg/kg, rats presented tremors 5 minutes after dermal application, and died within 30 minutes after clonic convulsions.
Interpretation of results:
Category 3 based on GHS criteria
Conclusions:

Catechol is classified as "toxic in contact with skin" in the GHS system (EU). The classification required under EU GHS Regulation is Acute. Tox. cat. 3, H311.
Executive summary:

In an acute dermal toxicity study (Rhône-Poulenc, 1973), CD male and female rats (5/sex/group) were dermally exposed to catechol for a maximum of 24 hours to their back, at doses of 125, 875 and 1125 mg/kg bw. Animals then were observed for 15 days.

 

Dermal LD50Combined=  600 mg/kg bw.

 

Catechol is toxic in contact with skin based on the LD50 in rats and according to EU GHS Regulation.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
600 mg/kg bw

Additional information

Oral route:

Four studies were available but two of them were retained: one as key study and another as supporting study because they were reliability 2.

The summary of the key study is the following:

In an acute oral toxicity study (Flickinger, 1967), groups of 5 albino male rats were given a single oral dose of catechol at doses of 0, 158, 316, 630 and 1260 mg/kg bw and observed for 14 days. No death occurred at 158 mg/kg bw, 2/5 died at 316 mg/kg bw and 5/5 at 630 mg/kg bw. No clinical signs were reported and the autopsy revealed for rats died during the study: hyperaemia of the stomach and intestines. None of the rats sacrificed at the end of the experiment revealed gross pathology during pathological examination.

  

Inhalation route:

In one study (Flickinger, 1976) with validity 2, 6 female Wistar rats were exposed to aerolizated solutions of catechol at nominal doses from 1.5, 2 and 2.8 mg/L for 8 hours. The LC0 was > 2.8 mg/L. At this dose, no mortality occurred, but effects were noted on central nervous system and loss of tail and toes. Similar tail loss occurred in 2/6 rats subjected to 2.0 mg/L aerosol. The loss of distal portions of the tail and accompanying loss of digits at doses of 2.8 and 2.0 mg/l was dose related. No clinic signs and/or similar tail loss occurred in the 6 rats exposed to 1.5 mg/L.

Dermal route:

Two studies were available, from one study report and from one publication. One was considered as key study and the second was considered a supporting study (both studies had reliability 2).

The summary of the study report is the following:

In an acute dermal toxicity study (Rhône-Poulenc, 1973), CD male and female rats (5/sex/group) were exposed to catechol by dermal route for a maximum of 24 hours to their back, at doses of 125, 875 and 1125 mg/kg bw. Animals then were observed for 15 days. 0/10 died at 125 mg/kg and no clinical signs, and 10/10 died at 875 and 1125 mg/kg, the rats presented tremors 5 minutes after dermal application, and died within 30 minutes after clonic convulsions.

In the second study the effects observed after dermal administration were local effects and death with an LD50 of 800 mg/kg bw.

 

Justification for classification or non-classification

Oral LD50 Males = 300 mg/kg bw (95% C.L. 200-500 mg/kg) Catechol is considered as toxic based on the LD50 obtained, and classified as category 3 (H301: Toxic if swallowed) according to classification criteria of EC Regulation 1272/2008.

Based on the LC0 (8h) > 2.8 mg/L and according to CLP Regulation criteria, catechol is not considered as harmful by inhalation after acute exposure. No classification is required.

Dermal LD50 Combined = 600 mg/kg bw. Catechol is considered as toxic in contact with the skin and should be classified as category 3 (H311: Toxic in contact with skin) according to classification criteria of EC regulation 1272/2008.

These classifications based on the availaible data are consistent with the harmonized classification (13th ATP of the CLP Regulation). This ATP was published in the EU official journal on 4 October 2018 and was enter into force 20 days after publication. This ATP has to be applied from 1 May 2020.