Phenylacetylene

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From October 29, 2021 to February 24, 2022

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Study performed according to OECD Guideline No.423 and under GLP compliance (GLP deviation due to the lack of verification of the the test item concentration in the dose applied during this test. Without impact on the reliability of the results generated).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2022

Report date:

2022

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

December 17th, 2001

Deviations:

yes

Remarks:

Daily examination carried at 50 hrs and 44 min, instead of at 48 ± 2 hrs after administration of the test item and relative humidity lower than 30% registered during 2 periods of the study. No impact on the conclusion of the study.

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Phenylacetylene

EC Number:

208-645-1

EC Name:

Phenylacetylene

Cas Number:

536-74-3

Molecular formula:

C8H6

IUPAC Name:

ethynylbenzene

Test material form:

liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

SPF Caw

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (F-69210 Saint-Germain-Nuelles)
- Age at study initiation: female (8 or 9 weeks old)
- Weight at study initiation: female (185-230 g)
- Housing: 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 : foodstuff (ENVIGO – 2914C / 2016). Food was removed on day 1 and then redistributed 4 hours after the test item administration
- Water : tap-water from public distribution system, ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature : 19°C to 25°C
- Humidity : 30% to 70%
- Air changes (per hr): 10 per hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

-Dose volume applied: 2.15 mL/kg
-Rationale: oral administration was used as this is one possible route of human exposure during manufacture, handling and use of the test article.

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

6 animals/dose

Control animals:

no

Details on study design:

The test item PHENYLACETYLENE was administered by gavage to a group of 6 female Sprague Dawley rats at the dose of 300 mg/kg body weight (step 1 and step 2), then a group of 6 female Sprague Dawley rats at the dose of 2000 mg/kg body weight (step 3 and step 4).

- Daily examination
Systematic examinations were carried out to identify any behavioural or toxic effects on the major physiological functions 30 minutes, 1 hour ± 6 minutes, 3 hours ± 30 minutes, 4 hours ± 30 minutes, 24 and 48 hours ± 2 hours after administration of the test item and continued daily for 14 days. This examination focuses particularly on a list of symptoms, recorded as "present" or "absent" on the observation sheet. These observations were compared to historical control data.
Observations and a mortality report were then carried out every day for 14 days.

- Periodical examinations
The animals were weighed on day D0 (just before administering the test item) then on day 2, day 7, and day 14. Weight changes were calculated and recorded. The body weight evolution of animals treated with the test item is compared with the body weight evolution of the control group.

- Examination at the end of the test
On Day 14, the animals were euthanized with sodium pentobarbital (Dolethal®). 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.

Results and discussion

Preliminary study:

None

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:

2 500 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was noted in animals treated at the dose of 300 mg/kg body weight (step 1 and step 2).
Two mortalities (1 animal in each step) were noted in animals treated at the dose of 2000 mg/kg body weight, on day 1.

Clinical signs:

other:

Body weight:

other body weight observations

Remarks:

The body weight evolution of the animals (treated at the dose of 300 mg/kg body weight) remained normal during the study.

Gross pathology:

The macroscopic examination of the animals (treated at the dose of 300 mg/kg body weight) at the end of the study did not reveal treatment related changes.

Any other information on results incl. tables

Group treated at 2000 mg/kg bw (Steps 3 and 4):
Two mortalities (1 animal in each step) were noted in animals treated at the dose of 2000 mg/kg body weight, on day 1. No clinical signs related to the administration of the test item were observed before the mortalities. The macroscopic examination of the animals revealed thin (2/2) and red (1/2) stomach wall with the stomach swollen with air (1/2). It was also noted areas of redness on proventricular wall, orange fundic wall (1/2) and air inside duodenum, jejunum and ileon (1/2).

 

In surviving animals of Step 3 (2/3), it was noted a decrease of spontaneous activity (2/2), a decrease of muscle tones (2/2) and mydriasis (1/2) from the first hours after the treatment. On day 1, a decrease of righting reflex (1/2), a loss of balance when walking (2/2) and an increase of lachrymation (2/2) were noted. Chromodacryorrhea (1/2) was also noted on day 2. The animals recovered a normal activity on day 2.

 

In surviving animals of Step 4 (2/3), it was noted a decrease or absence of spontaneous activity (2/2) and piloerection (2/2) from the first hours after the treatment until day 2. On day 1, a decrease of muscle tones (2/2), a decrease of Preyer’s reflex (2/2), an increase of lachrymation (2/2) and dyspnea (2/2) were noted. Chromodacryorrhea (2/2) was also observed from day 2 to day 5. The animals recovered a normal activity on day 6. The mean body weight evolution of the animal revealed a decrease of 5% of body weight at D2 versus D0. Then, the body weight evolution remains normal. The macroscopic examination of the animal at the end of the study did not reveal treatment related changes.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the oral LD50 of the test item PHENYLACETYLENE is higher than 2000 mg/kg body weight and lower than 5000 mg/kg body weight.
In accordance with the OECD Test Guideline No. 423, the LD50 cut-off of the test item may be considered as 2500 mg/kg body weight by oral route in the rat.
Therefore, the test item PHENYLACETYLENE is not classified according to the Regulation (EC) No. 1272/2008 (CLP) and no signal word or hazard statement is required.

Executive summary:

The test item PHENYLACETYLENE was administered to a group of 6 female Sprague Dawley rats at the dose of 300 mg/kg body weight, then a group of 6 female Sprague Dawley rats at the dose of 2000 mg/kg body weight.
The experimental protocol was established according to the official method as defined in the OECD Test Guideline No. 423 dated December 17th, 2001.

 

Group treated at 300 mg/kg (Steps 1 and 2):
No mortality was noted in animals treated at the dose of 300 mg/kg body weight.
No clinical signs related to the administration of the test item were observed during the study.
The body weight evolution of the animals remained normal during the study.
The macroscopic examination of the animal at the end of the study did not reveal treatment related changes.

 

Group treated at 2000 mg/kg (Steps 3 and 4):
- Two mortalities (1 animal in each step) were noted in animals treated at the dose of 2000 mg/kg body weight, on day 1. No clinical signs related to the administration of the test item were observed before the mortalities. The macroscopic examination of the animals revealed thin (2/2) and red (1/2) stomach wall with the stomach swollen with air (1/2). It was also noted areas of redness on proventricular wall, orange fundic wall (1/2) and air inside duodenum, jejunum and ileon (1/2).
- In surviving animals of Step 3 (2/3), it was noted a decrease of spontaneous activity (2/2), a decrease of muscle tones (2/2) and mydriasis (1/2) from the first hours after the treatment. On day 1, a decrease of righting reflex (1/2), a loss of balance when walking (2/2) and an increase of lachrymation (2/2) were noted. Chromodacryorrhea (1/2) was also noted on day 2. The animals recovered a normal activity on day 2.
- In surviving animals of Step 4 (2/3), it was noted a decrease or absence of spontaneous activity (2/2) and piloerection (2/2) from the first hours after the treatment until day 2. On day 1, a decrease of muscle tones (2/2), a decrease of Preyer’s reflex (2/2), an increase of lachrymation (2/2) and dyspnea (2/2) were noted. Chromodacryorrhea (2/2) was also observed from day 2 to day 5. The animals recovered a normal activity on day 6. The mean body weight evolution of the animal revealed a decrease of 5% of body weight at D2 versus D0. Then, the body weight evolution remains normal. The macroscopic examination of the animal at the end of the study did not reveal treatment related changes.

 

Under the test conditions, the oral LD50 of the test item PHENYLACETYLENE is higher than 2000 mg/kg body weight and lower than 5000 mg/kg body weight. In accordance with the OECD Test Guideline No. 423, the LD50 cut-off of the test item may be considered as 2500 mg/kg body weight by oral route in the rat.
Therefore, the test item PHENYLACETYLENE is not classified according to the Regulation (EC) No. 1272/2008 (CLP) and no signal word or hazard statement is required.