3-hydroxy-p-anisaldehyde

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

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:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3-hydroxy-p-anisaldehyde

EC Number:

210-694-9

EC Name:

3-hydroxy-p-anisaldehyde

Cas Number:

621-59-0

Molecular formula:

C8H8O3

IUPAC Name:

3-hydroxy-4-methoxybenzaldehyde

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Six Sprague Dawley rats (SPF Caw) supplied by Elevage JANVIER LABS (53940 Le Genest St Isle – France)
- Females nulliparous and non-pregnant: yes
- Age at study initiation: At the beginning of the study, the animals were 8-week old, with a mean body weight of 195 g (SD: 2.9).
- Fasting period before study: yes
- Housing: Healthy female rats were housed by 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): standard laboratory foodstuff (ENVIGO 2016) ad libitum.
- Water (e.g. ad libitum): Tap water ad libitum.
- Acclimation period: at least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25ºC
- Humidity (%): 30-70%
- Air changes (per hr): at least 10 times/hour
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark.

IN-LIFE DATES: From: 12/12/2017 - To: 27/12/2017

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

CLASS METHOD
- Rationale for the selection of the starting dose: As no information regarding the acute toxicity of the test item was available suggesting toxicity of the test item and in accordance with the principles of animal welfare, the first tested dose was 2000 mg/ kg b.w.

Doses:

Step 1: 2000 mg/kg bw.
Step 2: 2000 mg/kg bw.

No. of animals per sex per dose:

3 female rats were used in step 1 (Rf2182 to Rf2184) and 3 female rats in step 2 (Rf2185 to Rf2187)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Systematic examinations were carried out to identify any behavioural or toxic effects on the major physiological functions 30 min, 1h, 3h, 4h, 24h, 48h after administration of the test item and continued daily during 14 days. Weight was determined on day 0 (directly before administration), 2, 7 and 14 before euthanasia.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross examinations.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study.

Clinical signs:

other: A decrease in spontaneous activity (6/6), muscle tones (3/6), righting reflex (3/6), Preyer’s reflex (3/6) associated with hypothermia (3/6), an increase of salivation (3/6), piloerection (1/6), noisy breathing (2/6) and nasal secretions (1/6) were noted

Gross pathology:

The macroscopic examination of the animals at the end of the study did not reveal treatment related changes.

Any other information on results incl. tables

Table 1. Body weights and weight gain of the animals (grams)

FEMALES	D0	D2	D2-D0	D7	D7-D0	D14	D14-D0
Rf 2182 Rf 2183 Rf 2184	201 193 195	220 202 208	19 9 13	231 232 228	30 39 33	246 245 250	45 52 55
Rf 2185 Rf 2186 Rf 2187	194 196 194	195 188 161	1 -8 -33	218 221 222	24 25 28	240 249 245	46 53 51
MEAN Standard deviation	195.5 2.9	195.7 20.2	0.2 18.8.	225.3 5.8	29.8 5.6	245.8 3.5	50.3 4.0

 

Table 2. Clinical signs, overall list.

Dose (mg/kg bw)	Time	Mortality	Step 1. Animal Rf.			Step 2. Animal Rf.
			2182	2183	2184	2185	2186	2187
2000	30 min	0	N	N	N	SIGNS	SIGNS	SIGNS
	1 h	0	SIGNS	SIGNS	SIGNS	SIGNS	SIGNS	SIGNS
	3 h	0	SIGNS	SIGNS	SIGNS	N	N	N
	4 h	0	SIGNS	SIGNS	SIGNS	N	N	N
	D1	0	N	N	N	N	N	SIGNS
	D2-D4	0	N	N	N	N	N	N
	D5-D14	0	N	N	N	N	N	N
Remarks	30min		Rf2186, 2187: noisy breathing Rf2186: nasal secretions, little regurgitation.
	1h - 4h, D1-D4		Rf2186, 2187: noisy breathing
	D5-D14		none

 

Table 3. Necropsy findings, overall list.

Observations	Step 1 Animals Rf2182-2184	Step 2 Animals Rf2185-2187
General Appearance	Normal	Normal
Oesophagus	NtR	NtR
Stomach	NtR	NtR
Duodenum	NtR	NtR
Jejunum	NtR	NtR
Ileon	NtR	NtR
Caecum	NtR	NtR
Colon	NtR	NtR
Rectum	NtR	NtR
Spleen	NtR	NtR
Liver	NtR	NtR
Thymus	NtR	NtR
Trachea	NtR	NtR
Lungs	NtR	NtR
Heart	NtR	NtR
Kidneys	NtR	NtR
Urinary Bladder	NtR	NtR
Overies	NtR	NtR
Uterus	NtR	NtR
Adrenals	NtR	NtR
Pancreas	NtR	NtR
Particulars	None	None

 *NtR: Nothing to report.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

EU criteria

Conclusions:

The oral LD50 of the test item in female rats was greater thatn 2000 mg/kg bw. The LD50 cut-off of the test item may be considered to be higher than 5000 mg/kg bw.

Executive summary:

The potential acute toxicity of the test item was studied on female Sprague-Dawley rats, according to OECD TG 423, under GLP conditions. Since no data indicating acute toxicity was available, a first step was performed by administering a single dose of 2000 mg/kg bw test item to three animals by gavage. As no mortality was observed, a second step was performed by dosing three additional animals with the same dose. No mortality occurred during the study. A decrease in spontaneous activity (6/6), muscle tones (3/6), righting reflex (3/6), Preyer’s reflex (3/6)associated with hypothermia (3/6), an increase of salivation (3/6), piloerection (1/6), noisy breathing (2/6) and nasal secretions (1/6) were noted during the first hours of the test. The animals recovered a normal activity between days 1 and 5. An absence of body weight gain was noted on day 2 versus day 0. Then, the body weight evolution of the animals was normal. The macroscopic examination of the animals at the end of the study did not reveal treatment related changes. Based on the results, the oral LD50 was found to be > 2000 mg/kg bw. In accordance with the OECD TG 423, the LD50 cut-off of the test item may be considered to be higher than 5000 mg/ kg body weight by oral route in the rat.