3,4-dihydroxybenzaldehyde

Endpoint summary

Description of key information

Acute oral toxicity: Key study. Test method according to OECD 423, GLP study. The LD50 of the test item is higher than 300 mg/kg and lower than 2000 mg/ kg body weight by oral route in the rat. Therefore test item has to be classified in Category 4 in accordance with the Regulation EC No. 1272/2008.

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:

19 July to 16 August 2022

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)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (F-69210 Saint-Germain-Nuelles)
- Females: 9
- Age at study initiation: 8 weeks
- Period before study: 5 days.
- Housing: housed bu group of three in solid-bottomed clear polycarbonate cages with a stainless-steel mesh lid. Each cage contains sawdust bedding which was changed at least 2 times a week. Each cage was installed in conventional air-conditioned animal husbandry.
- Diet (e.g. ad libitum): removed on Day 1 and then redistributed 4 hous after the test item administration.
- Water (e.g. ad libitum): Ad libitum. Drinking water (tap-water from public distribution system).
- Acclimation period: the animals were acclimatized for at least 5 days before treatment.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19ºC to 25ºC
- Humidity (%): 30 to 70%
- Air changes (per hr): ≥ 10 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours light (07.00 to 19.00) and 12 hours dark cycle.

Route of administration:

oral: gavage

Vehicle:

DMSO

Details on oral exposure:

The test item was used after being diluted in DMSO.
DMSO (vehicle) was chosen as it produced the most suitable formulation at the requested dose of 300 mg/kg body weight.

Doses:

2000 mg/kg and 300 mg/kg

No. of animals per sex per dose:

2000 mg/kg (3 female rats) and 300 mg/kg (6 female rats)

Control animals:

yes

Remarks:

Study performed on three animals receiving DMSO under requirements of OECD Guideline 423.

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the animals were observed in day 0, 2, 7 and 14.
- Necropsy of survivors performed: yes.
- Clinical signs including body weight: spontaneous activity, Preyer’s reflex (noise), respiratory rate, convulsions, tremors, body temperature, muscle tone, palpebral opening, pupil appearance, salivation, lachrymation, righting reflex, back hair appearance. The body weight evolution of animals treated with the test item was compared with the body weight evolution of the control group.
- Other examinations performed: Macroscopic observations were entered on individual autopsy sheets. Only those organs likely to be modified in cases of acute toxicity were examined. No organ was removed and preserved in view to microscopic examinations.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

2 mortalities were noted in animals treated at the dose of 2000 mg/kg body weightt 1 hour after the treatment. No mortality was noted in animals treated at the dose of 300 mg/kg body weight

Clinical signs:

other:

Body weight:

other body weight observations

Remarks:

Group treated at 2000 mg/kg and group treated at 300 mg/kg body weight remained normal

Gross pathology:

- Group treated at 2000 mg/kg: in ded animals the macroscopic examination of the animals revealed a rigor mortis, wet hairs on the muzzle, a stomach filled with air, a thin proventricular wall, a brown/orange and thick fundic mucosa with red areas and a brown and a thin fundic mucosa with red areas. In the surving ones, the macroscopic examination did not reveal any treatment related changes.
- Group treated at 300 mg/kg: the macroscopic examination of the animals at the end of the study evealed a thinning of the proventricular well in two animals

FEMALES	D0	D2	D2-D0	D7	D7-D0	D14	D14-D0
Rf 6950	210	-	-	-	-	-	-
Rf 6951	207	214	7	264	57	287	80
Rf 6952	210	-	-	-	-	-	-
MEAN	209.0	214.0	7.0	264.0	57.0	287.0	80.0
Standard deviation	1.7	-	-	-	-	-	-

Dose: 2000 mg/kg body weight 

	D0	D2	D2-D0	D7	D7-D0	D14	D14-D0
Rf 6953	210	230	20	251	41	247	37
Rf 6954	211	224	13	244	33	240	29
Rf 6955	218	244	26	261	43	263	45
Rf 6959	180	176	-4	180	0	211	31
Rf 6960	184	172	-12	223	39	238	54
Rf 6961	219	192	-27	258	39	272	53
MEAN	203.7	206.3	2.7	236.2	32.5	245.2	41.5
Standard deviation	17.2	30.3	20.5	30.7	16.3	21.4	10.8

Dose: 300 mg/kg body weight 

Interpretation of results:

other: Category 4 (CLP Regulation EC no. 1272/2008)

Conclusions:

The LD50 of the test item is higher than 300 mg/ kg body weight and lower than 2000 mg/kg body weight by oral route in the rat.

Executive summary:

The acute oral toxicity of the test item has been tested in accordance with OECD Test Guideline 423, following GLP. 9 female Sprague-Dawley rats were administered by oral gavage in 3 steps with test item diluted in vehicle DMSO.

The study was performed with 3 female rats at 2000 mg/kg (Step 1), with 3 female rats at 300 mg/kg (Step 2) and with 3 female rats at 300 mg/Kg (Step 3). 

In group treated at 2000 mg/kg, two mortalities were noted in animals treated at the dose of 2000 mg/kg weight 1 hout after the treatment. the body weight of the animal remained normal during study. The macroscopic examination of the animals at the end of the study did not reveal treatment related changes.

In group treated at 300 mg/kg, no mortality was noted in animals. The body weight of the animal remained normal during study. The macrscopis examination of the niamals at the end of the study revealed a thinning of the proventricular well in two animals.

Based on these results, the LD50 of the test item is determined to be higher than 300 mg/kg and lower than 2000 mg/ kg bw by oral route in the rat.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

>= 300 - <= 2 000 mg/kg bw

Quality of whole database:

Key study with Klimisch score = 1

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the available data, the substance is classified as Category 4 for acute toxicity (oral) according to CLP Regulation (EC) no. 1272/2008.