Octahydro-2H-1-benzopyran-2-one

Endpoint summary

Description of key information

Acute oral (OECDTG401): no adverse effect observed

Acute dermal (OECDTG402): no adverse effect observed

Acute inhalation (Route to route extrapolation): no adverse effect predicted

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:

Not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Reliability has been presented as 2 because similar to OECD Guideline protocol has been followed but not GLP.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

no details on test material (purity not indicated), no details on test animals and environmental conditions, observation period unknown (only until day 5 included in report).

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
No details.

ENVIRONMENTAL CONDITIONS
No details.

Route of administration:

oral: unspecified

Vehicle:

not specified

Details on oral exposure:

No details.

Doses:

1730, 2470, 3510 and 5000 mg/kg bw

No. of animals per sex per dose:

1730 mg/kg bw: total 20 (no sex specified)
2470, 3510 and 5000 mg/kg bw: 10 (no sex specified)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 5 days
- Frequency of observations and weighing: No data
- Necropsy of survivors performed: yes

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

3 900 mg/kg bw

Based on:

test mat.

95% CL:

2 600 - 5 900

Mortality:

See "any other information results"

Clinical signs:

other: 1730 mg/kg bw: Lethargy, chromorhynorrhea, piloerection, ptosis and diarrhea. 2470 mg/kg bw: Lethargy and flaccid muscle tone. 3510 mg/kg bw: Lethargy, chromorhynorrhea and piloerection. 5000 mg/kg bw: Lethargy, chromorhynorrhea, piloerection, ataxia, red

Deaths per day after exposure to Bicyclononalactone

Dose mg/kg	Deaths/day	total
1730	3/0, 1/1, 1/2, 1/5	6/20
2470	1/0, 2/1	3/10
3510	2/0, 1/1, 1/4	4/10
5000	3/0, 3/1	6/10

Necropsy observations after exposure to Bicyclononalactone

	No. of rats
Doses mg/kg bw	1730	2470	3510	5000
Normal	8	2		1
Cannabalized			2
Exudate, nose/mouth, red	2	3		2
Exudate, nose/mouth, yellow	1	1		3
Exudate, anogenital, brown	1
Exudate, anogenital, yellow	2
Exudate, nose/mouth, clear			1	2
Intestines, areas red
Intestines, areas yellow	4	4	1	9
Intestines, bloated	1
Stomach, areas red	1	1
Liver dark	8		2	4
Liver mottled		1	6	2
Lungs dark	1	3	2	4
Lungs areas dark	1	3		2
Consolidation of left lung *				1
Kidney dark	9	3	2	4
Kidney mottled	1		4
Spleen dark	2
Spleen large	2			4
Spleen, tip darker than normal		1
Bladder, contained blood			1	2

* Hardened texture to lung tissue w/ yellowish nodules troughout.

Interpretation of results:

other: Not acute harmful.

Remarks:

According to Regulation (EC) No. 1272/2008 and its amendments.

Conclusions:

An LD50 of 3900 mg/kg bw was obtained in the acute oral toxicity study with rats. According to GHS the substance needs to be classified for acute oral toxicity category 5 and labelled with H103: May be harmful if swallowed.

Executive summary:

In an acute oral toxicity study 4 groups of 10 rats were orally exposed to 1730, 2470, 3510 and 5000 mg/kg bw of the substance. The rats were observed for signs of toxicity and pharmacological effects for a period of 5 days. Deaths occurred on day 0, 1, 2, 4 and 5. Lethargy was seen at all levels, other clinical signs were chromorhynorrhea, piloerection, ataxia, red exudate, ptosis, diarrhea, falccid muscle tone and anogenital.

Based on the results, an LD50 of 3900 mg/kg bw was obtained in the acute oral toxicity study with rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The acute oral toxicity result is of sufficient quality and adequate for this dossier.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

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

Study period:

Not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The reliability score is based on the study is similar to current OECD guideline but not GLP.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

no details on test material (purity not indicated), no details on test animals and environmental conditions, observation period unknown (only until day 5 included in report), no details on dermal exposure.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
No details.

ENVIRONMENTAL CONDITIONS
No details.

Type of coverage:

not specified

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

No details specified.

Duration of exposure:

No details.

Doses:

1250, 2500 and 5000 mg/kg bw

No. of animals per sex per dose:

Total of 4 (sex not specified).

Control animals:

no

Details on study design:

- Duration of observation period following administration: 5 days
- Frequency of observations and weighing: No data
- Necropsy of survivors performed: yes

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

3 500 mg/kg bw

Based on:

test mat.

95% CL:

2 200 - 5 700

Mortality:

See "any other information results"

Clinical signs:

other: At 2500 mg/kg bw lethargy was observed in one animal on day 1. All other animals showed no abnormalities at any dose level.

Gross pathology:

See "any other information results"

Other findings:

Irritation: See "any other information results"

Deaths per day after exposure to Bicyclononalactone

Dose mg/kg bw	Deaths/day	total
1250	0	0/4
2500	1/1	1/4
5000	2/1, 1/2	3/4

Skin irritation after exposure to Bicyclononalactone

Dose mg/kg bw	1250	2500	5000
Redness:
Slight		1/3 *	1/2 **
Moderate	4/4	2/3	1/2
Edema:
Slight	4/4	3/3	2/2

* 1 animal dead prior to reading

** 2 animals dead prior to reading

Necropsy observations after exposure to Bicyclononalactone

	No. of rats
Doses mg/kg bw	1250	2500	5000
Normal		2	1
Exudate, nose/mouth, yellow			1
Exudate, anogenital, brown		1	2
Intestines, areas red		1	3
Intestines, areas yellow			1
Intestines, bloated	3	1	3
Stomach, areas red			1
Liver dark	3	1
Liver mottled		1	3
Lungs dark			2
Lungs areas dark		1	1
Kidney dark	1		1
Kidney mottled	2
Skin edema			2
Skin redness			2
Intestines, contained green fluid			1
Liver white nodules			1
Gall bladder large		1
Kidney pale			1

Interpretation of results:

other: Not acute harmful.

Remarks:

According to Regulation (EC) No. 1272/2008 and its amendments.

Conclusions:

An LD50 of 3500 mg/kg bw was obtained in the acute dermal toxicity study with rabbits. According to GHS the substance needs to be classified for acute dermal toxicity category 5 and labelled with H313: May be harmful in contact with skin.

Executive summary:

In an acute dermal toxicity study 3 groups of 4 rabbits were dermally exposed to 1250, 2500 and 5000 mg/kg bw of Bicyclononalactone. The rabbits were observed for signs of toxicity and pharmacological effects for a period of 5 days. Deaths occurred on day 1 and 2. At 2500 mg/kg bw lethargy was observed in one animal on day 1 and one animal died. At 5000 mg/kg bw 3/4 animals died by day 2. Slight to moderate redness and slight edema was observed in all animals. Based on the results, an LD50 of 3500 mg/kg bw was obtained in the acute dermal toxicity study with rabbits.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The acute dermal toxicity result is of sufficient quality and adequate for this dossier.

Additional information

Acute oral toxicity: In an acute oral toxicity study 4 groups of 10 rats were orally exposed to 1730, 2470, 3510 and 5000 mg/kg bw of the substance. The rats were observed for signs of toxicity and pharmacological effects for a period of 5 days. Deaths occurred on day 0, 1, 2, 4 and 5. Lethargy was seen at all levels, other clinical signs were chromorhynorrhea, piloerection, ataxia, red exudate, ptosis, diarrhea, falccid muscle tone and anogenital.

Based on the results, an LD50 of 3900 mg/kg bw was obtained in the acute oral toxicity study with rats.

Acute inhalation: Acute inhalation is predicted based on the acute oral toxicity in accordance with the ECHA CLP guidance document (2015, 3.1.3.3.4: 1 mg/kg bw = 0.0052 mg/l (5.2 mg/m3). The acute inhalation is predicted to be 10140 mg/m3 (using 100% inhalation and 50% oral absorption). The calculated saturated vapour pressure is 13.3 mg/m3 (MW in mg*VP in Pa/ 8.3 (gas constant*293oK). This means that the acute inhalation concentration cannot be reached and therefore no acute inhalation toxicity is anticipated.

Acute dermal toxicity: In an acute dermal toxicity study 3 groups of 4 rabbits were dermally exposed to 1250, 2500 and 5000 mg/kg bw of Bicyclononalactone. The rabbits were observed for signs of toxicity and pharmacological effects for a period of 5 days. Deaths occurred on day 1 and 2. At 2500 mg/kg bw lethargy was observed in one animal on day 1 and one animal died. At 5000 mg/kg bw 3/4 animals died by day 2. Slight to moderate redness and slight edema was observed in all animals. Based on the results, an LD50 of 3500 mg/kg bw was obtained in the acute dermal toxicity study with rabbits.

Justification for classification or non-classification

The substance does not have to be classified for acute toxicity by the oral, inhalation and dermal route according to Regulation (EC) No. 1272/2008 and its amendments .