Reaction mass of benzoyl chloride, toluoyl chloride and 2-methyl resorcinol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11-May-2021 to 09-June-2021 (experimental dates)

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2021

Report date:

2021

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

17 December 2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of benzoyl chloride, toluoyl chloride and 2-methyl resorcinol

Molecular formula:

not applicable

IUPAC Name:

Reaction mass of benzoyl chloride, toluoyl chloride and 2-methyl resorcinol

Test material form:

solid: particulate/powder

Details on test material:

Appearance: beige powder

Specific details on test material used for the study:

Appearance: Light brown powder
Storage Conditions: stored at 15-25°C

Test animals

Species:

rat

Strain:

other: Crl:WI(Han)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd., Margate
- Females nulliparous and non-pregnant: yes
- Age at study initiation: approximately 9 to 11 weeks
- Weight at study initiation: 157 to 186 g
- Fasting period before study: yes (from the evening of the day prior to dosing (Day 1) until approximately 3 hours after dosing)
- Housing: in groups of up to five

- Acclimation period: 7 to 15 days
No contaminants were present in bedding, water or feed at levels which might have interfered with achieving the objective of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 40-70
- Air changes (per hr): minimum of 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From 11 May 2021 to 09 June 2021

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

Test Article Formulation
Dose levels were expressed gravimetrically (considered as 100% pure). The test article was dispersed in corn oil because the test article did not dissolve / suspend in purified water or 1% w/v aqueous methylcellulose. All formulations were used within two hours of preparation. The formulations were maintained on a magnetic stirrer or were repeatedly inverted prior to administration to ensure homogeneity.
Doses were administered orally, by gavage, using plastic syringes and rubber catheters. Each rat was dosed once on Day 1, by passing the tip of a catheter along the esophagus and instilling the test article into the gastric lumen.
Individual doses (mL) were calculated using the fasted body weights of the rats on the morning of dosing (Day 1) and the dose volume of 10 mL/kg bw.

Doses:

Main study: 2000 mg/kg bw; Preliminary test: 300 mg/kg bw and 2000 mg/kg bw

No. of animals per sex per dose:

Main study: 4 females; Preliminary test: 1 female/group

Control animals:

no

Details on study design:

Treated rats were observed closely for clinical signs of reaction to treatment. Clinical signs were recorded immediately post-dose, at approximately 15 and 30 minutes post-dose, hourly between 1 and 4 hours post-dose (inclusive), twice daily on Days 2, 3 and 4 and once daily from the fifth to last day of the observation period. Individual records of clinical signs were maintained for each treated rat. Rats were weighed on Day 1 (day before dosing) and on Days 1, 4, 8 and 15.
Rats were killed on Day 15. Each animal was given isoflurane anesthesia and was exsanguinated by the severing of major blood vessels. After exsanguination a full macroscopic necropsy was performed and all lesions were recorded.
The necropsy procedure included inspection of external surfaces and orifices, all viscera and tissue within the abdominal, thoracic and cranial cavities, free-hand sectioning of the liver and kidneys and examination of representative sections of mucosal surfaces of the stomach, small and large intestines.

Results and discussion

Preliminary study:

Since there were no deaths in the preliminary study, a further four fasted females were given a single oral dose of test article at a dose level of 2000 mg/kg body weight.

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other:

Body weight:

other body weight observations

Remarks:

All rats gained weight during the first and second weeks of the observation period, with the exception of one animal that showed a slight loss of body weight during the second week of the observation period (details given bellow).

Gross pathology:

No abnormalities were noted at necropsy.

Any other information on results incl. tables

Table 1: Individual Body Weights and Weekly Increments

Dose Level (mg/kg)	Animal Number	Body weight (g) Day -1	Body weight (g) Day 1	Body weight (g) Day 4	Body weight (g) Day 8	Body weight (g) Day 15	Increment (g) Day 1 to 8	Increment (g) Day 8 to 15
300	237	170	157	168	178	185	21	7
2000	238	196	186	204	206	215	20	9
2000	239	189	179	193	201	203	22	2
2000	240	184	172	185	190	191	18	1
2000	241	170	168	186	194	193	26	-1
2000	242	190	175	194	193	204	18	11

A minus symbol [-] indicates a body weight loss

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of an acute oral (fixed dose) test, performed according to OECD/EC guidelines and GLP principles, the acute oral LD50 of the test article, BTMR, was was found to be >2000 mg/kg bw.

Executive summary:

An acute oral (fixed dose) test was performed according to OECD/EC guidelines a nd GLP principles with BTMR. In the preliminary study fasted female rats were given the test article as a single dose by oral gavage at dose levels of 300 and 2000 mg/kg. Since there were no deaths in the preliminary study, a further four fasted females were given a single oral dose of test article at a dose level of 2000 mg/kg body weight. The test article was dispersed in corn oil and administered at a dose volume of 10 mL/kg. All animals were killed on Day 15 and subsequently underwent a full necropsy.

There were no deaths and no clinical signs of toxicity. All rats gained weight during the first and second weeks of the observation period, with the exception of one animal that showed a slight loss of body weight during the second week of the observation period. No abnormalities were noted at necropsy.

Acute oral LD50 of BTMR was found to be >2000 mg/kg bw.