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Administrative data

Description of key information

LD50 oral rat 140 mg/kg bw.  Temperature dependent increase of mortality after 8 hours inhalation exposure.  LD50 dermal >2000 mg/kg bw.

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:
1973
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: early study report, scientifically acceptable
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
according to BASF-internal standard
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Gassner
Sex:
male/female
Details on test animals and environmental conditions:
Mean body weights for male animals 202 g, for female animals 174 g
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
The test substance was administered as a 16%, 2% or 1% aqueous solution.
Doses:
50, 100, 125, 160, 200, 1600 µL/kg bw
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 7 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Sex:
male/female
Dose descriptor:
approximate LD50
Effect level:
140 other: µl/kg
Based on:
test mat.
Mortality:
50 and 100 µL/kg bw: no mortalities
125 µL/kg bw: 1/5 males and 0/5 females after 7 days
160 µL/kg bw: 5/5 males and 2/5 females after 7 days
200 µL/kg bw: 4/5 males and 5/5 females after 7 days
1600 µL/kg bw: 5/5 males and 5/5 females after 7 days
Clinical signs:
apathy, dyspnea
Gross pathology:
acute heart dilatation, acute congestive hyperemia; liver: loam-grey spotted with blunted margins; kidneys: brightened complexion; stomach: bloody ulcerations, ascites, slight lung edema.

µL = mg (densitiy 0.996 g/mL)

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
140 mg/kg bw
Quality of whole database:
One early study report which is scientifically acceptable and three supporting studies as read-across available are available.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1971
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non GLP, predated OECD guideline, but scientifically fully acceptable and well documented
Qualifier:
no guideline followed
Principles of method if other than guideline:
BASF- Test:acute inhalation toxicity with rats exposed to a saturated atmosphere for max. 8h
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Sex:
not specified
Route of administration:
inhalation
Type of inhalation exposure:
not specified
Vehicle:
air
Remarks:
200 L/h
Analytical verification of test atmosphere concentrations:
no
Remarks on duration:
1 - 8 h
Concentrations:
saturated atmosphere
No. of animals per sex per dose:
20°C: 12 for the 8-hour exposure
40°C: 12 for the 1-hour exposure, 6 for the 3-hour exposure and 6 for the 8-hour exposure
Control animals:
no
Details on study design:
The test substance was offered as a vapour at 20°C resp. 40°C.
Sex:
not specified
Dose descriptor:
other: Lethality
Based on:
test mat.
Exp. duration:
1 h
Remarks on result:
other: Mortality 0/12 (40°C)
Sex:
not specified
Dose descriptor:
other: Lethality
Based on:
test mat.
Exp. duration:
3 h
Remarks on result:
other: Mortality 3/6 (40°C)
Sex:
not specified
Dose descriptor:
other: Lethality
Based on:
test mat.
Exp. duration:
8 h
Remarks on result:
other: Mortality 6/6 (40°C)
Mortality:
20°C: no deaths after 8 hours.
40°C: no deaths after 1-hour exposure, 3 animals died after 3-hour exposure and all (6) animals died after 8-hour exposure.
Clinical signs:
Attemption to escape, irritation of the mucous membrane at 20°C.
Attemption to escape, irritation of the mucous membrane, dyspnea, apathy, staggering and tremor at 40°C.
Gross pathology:
Pulmonary congestion, congestion in the liver, degeneration of the liver, heart dilatation.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
One non GLP, predated OECD guideline study and three supporting studies available.

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:
February 13, 2002 until July 08, 2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes (incl. certificate)
Remarks:
testing lab.
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Young adult animals with a comparable weight were used. The acclimatization period was at least one week.
The animals were housed in fully air-conditioned rooms with central air-conditioning in a range of 20 - 24°C for temperature and of 30 - 70% for relative humidity. The day/night rhythm was 12 hours dark and 12 hours light. The animals were singly housed in stainless steel wire mesh cages.
Animal identification was done by cage cards and tail marking. A standardized animal diet and drinking water were available ad libitum.
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Single application to the clipped epidermis (dorsal and dorsolateral parts of the trunk); covering of the application site with a semi-occlusive dressing (the bandage consists of 4 layers absorbent gauze, Ph. Eur. Lohmann GmbH & Co. KG and Fixomull stretch (adhesive fleece), Beiersdorf AG) for 24 hours, afterwards removal of the dressing. Rinsing of the application site with warm water.
Clipping of the fur about 24 hours before the beginning of the study.
Application area: about 40 cm2
Duration of exposure:
single application
Doses:
2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Body weight determination: Individual body weights shortly before application (day 0), weekly thereafter and at the end of the study .
Signs and symptoms: Recording of signs and symptoms several times on the day of administration, at least once each workday for the individual animals.
Scoring of skin findings: Individual readings 30 - 60 minutes after removal of the semiocclusive dressing (day 1), as a rule weekly thereafter and at the end of the study (last day of the observation period).
Assessment of skin findings: According to Draize, J .H . (1959): Appraisal of the safety of chemicals in foods, drugs and cosmetics. The association of food and drug officials of the United States Austin, Texas.
Mortality: A check for any dead or moribund animal was made twice each workday and once on Saturdays, Sundays and on public holidays.
Pathology: Necropsy with gross-pathology examination on the last day of the observation period after killing with C02.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
none
Clinical signs:
Male animals:
No signs of systemic toxicity were observed during clinical examination.
Skin effects at the application site comprised well-defined erythema to moderate to severe erythema, erythema extending beyond the area of exposure, slight edema to moderate edema, edema extending beyond the area of exposure, application area distinct yellow discolored, bleeding at the inferior edge of the application area (diameter about 0.5 cm), petechiae, petechiae at the inferior edge of the application area (diameter about 1.5 cm), eczematoid skin change at the inferior edge of the application area (diameter about 1 cm up to 2 cm), due to complete detached crust in the region of eczematoid skin change the skin underneath appeared sleek and were observed on study day 1 and persisted until including study day 14.

Female animals:
No signs of systemic toxicity were observed during clinical examination.
Skin effects at the application site comprised well-defined erythema to moderate to severe erythema, erythema extending beyond the area of exposure, very slight edema to moderate edema, edema extending beyond the area of exposure, application area distinct yellow discolored, brownish discolored parts at the inferior edge of the application area, bleeding, bleeding extending beyond the area of exposure, bleeding at the inferior edge of the application area (diameter about 0 .5 cm), petechiae, eczematoid skin change extending beyond the area of exposure, eczematoid skin change at the inferior edge of the application area (diameter about 2 cm), due to complete detached skin in the region of eczematoid skin change the skin underneath apperared sleek like a scar and reddened and were observed on study day 1 and persisted until including study day 14.

Body weight:
The mean body weights of the animals increased throughout the study period.
Gross pathology:
No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study, except in the skin of the application site, where few skin lesions with incrusted surface were observed (three male and all female animals).
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
One GLP and guideline compliant study and two supporting studies as read-across available.

Additional information

Acute toxicity: oral

In the key study performed in rats (BASF 1973) the test item was assessed for acute oral toxicity . The test item was administered by oral gavage in doses of 50, 100, 125, 160, 200, and 1600 µL/kg. The day following exposure all animals of the 1600 µL/kg bw group were dead. Further deaths were noted in the remaining groups. On the 7th day of the observation period 4 male and 5 female rats of the 200 µL/kg group, 5 male and 2 female rats of the 160 µl/kg group and 1 male of the 125 µL/kg group were dead. Based on the results of the study the oral LD50 value for Hex-3 -yne-2,5 -diol was determined to be 140 µL/kg (140 mg/kg bw). In a supporting study (BASF 1971) the test item was assessed for acute oral toxicity in a non-GLP study in rats. The test item was administered by oral gavage in doses of 100, 125, 160, 200, 250, 320, 400, 500 and 640 mg/kg bw. 24 hours after administration of the test item mortalities were noted the 320, 400, 500 and 640 mg/kg bw groups. The observation period lasted for 7 days. At the end of the study 9 male and 10 female rats of the 640 mg/kg bw group, 9 male and 9 female rats of the 500 mg/kg bw group, 6 male and 6 female rats of the 400 mg/kg bw group and 1 male and 6 female of the 320 mg/kg bw dose group were dead. Based on the results the LD50 for acute oral toxicity was determined to be 380 mg/kg bw. In the following supporting studies (BASF 1958/ 1958) LD50 values of 200 µL/kg bw and 90 µL/kg bw were determined in rat respectively in mice.

Acute toxicity: inhalation

In the key study (BASF 1971) three time tests were performed in male and female rats including exposure for 1, 3 and 8 hours to a test item saturated atmosphere. In the 3 hour experiment 3 animals died on day 2 of the observation period. After 8 hour exposure at 40°C all animals (6) died. No mortalities were noted during the 1 hour test. A LC50 value was not reported. In a supporting study (Fraunhofer Gesellschaft 1979) the acute toxicity of the test item was assessed in 10 male and 10 female rats. The animals were exposed to a concentration of 5.5 mg/L (highest technically achievable concentration) for 1 hour. No mortality was observed during testing. The LC50 for the test item was determined to be > 5.5 mg/L. In two other supporting studies (BASF1973/ 1958) rats were exposed for 8 hours to a saturated atmosphere of test item. No mortalities were observed during the course of the studies.

Acute toxicity: dermal

The acute dermal toxicity of the test item was assessed in a study performed in rats according to OECD Guideline 402 (BASF 2002). 5 male and 5 female rats were exposed to a single dose of 2000 mg/kg bw in a semi-occlusive dressing for 24 hours. No mortality was observed during testing. Based on the results obtained from testing the dermal LD50 value of the test item was determined to be >2000 mg/kg bw. In two supporting studies performed in rabbits (BASF 1977/1979) LD50 values of > 200 mg/kg bw were determined. No mortality was observed during testing and the results of the key study were thus confirmed

Acute toxicity: other routes

The acute toxicity of the test item was further assessed in three studies after i.p. injection performed in mice (BASF 1973/1971/1958). The studies revealed LD50 values of 125 mg/kg bw, 90 mg/kg bw and 60 mg/kg bw. Additionally, information on intraveneous injection was available from a study performed in rabbits. The animals were treated with doses of 10, 20, 50, and 100 µL/kg bw. All animals of the 100 µL/kg bw group died during the first day, no other mortalities occured. A LD50 value was not reported. Further, information on acute toxicity after subcutaneous treatment of mice was available. Based on the results obtained from testing a LD50 value of 100 mg/kg bw was determined by interpolation. In the RTEC database a LDLo value of 500 mg/kg bw after i.p. injection in mice was noted.


Justification for selection of acute toxicity – oral endpoint
Only a early study report which is scientifically acceptable is available.

Justification for selection of acute toxicity – inhalation endpoint
Only a non GLP, predated OECD guideline, but scientifically fully acceptable and well documented study available.

Justification for selection of acute toxicity – dermal endpoint
GLP and guideline compliant study.

Justification for classification or non-classification

Based on the available data Hex-3-yn-2,5-diol was classified as R25 “toxic if swallowed” (Directive 67/548/EEC) and Cat. 3/ H301 “toxic if swallowed” (Regulation 1272/2008/EC (CLP)). No classification and labelling are necessary concerning acute dermal and inhalation toxicity.