Registration Dossier

Administrative data

Description of key information

Oral: The acute oral LD50 was determined to be > 2000 mg/kg bw in rats. 
Dermal: The acute dermal LD50 was determined to be > 5000 mg/kg bw in rats.

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:
1989-11-14 to 1989-11-29
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study similar to guideline but without GLP
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: DR. K. THOMAE GMBH, D-7950 BIBERACH, FRG
- Age at study initiation: young adult animals
- Weight at study initiation: 172 g for males and females
- Fasting period before study: about 16 h before administration
- Housing: stainless steel wire mesh cages, type DK-III (BECKER & CO., CASTROP-RAUXEL, FRG )
- Diet (e.g. ad libitum): ad libitum (KLIBA-LABORDIAET 343, KLINGENTALMUEHLE AG CH-4303 KAISERAUGST, SWITZERLAND)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12 H/12 H (6.00 - 18.00 HOURS/ 18.00 - 6.00 HOURS)
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
Administration volume: 10 mL/kg

Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males, 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: recording of signs and symptoms several times on the day of administration. At least once each work day. Check for moribund and dead animals twice each workday and once on holidays. Weighing on days 7 and 13.
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality noted.
Clinical signs:
No clinical signs noted.
Body weight:
No influence on body weight noted.
Gross pathology:
No pathologic findings noted.
Other findings:
None
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
Similar to guideline study, whole database factor: 1.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study 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:
2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline Study OECD 402 with GLP compliance
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: male animals approx. 8 weeks, female animals approx. 12 weeks
- Weight at study initiation: 200-250 g
- Fasting period before study: No
- Housing: single
- Diet: VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany
- Water: Tap water, ad libitum
- Acclimation period: Acclimatization period of at least 5 days before the beginning of the experimental phase; during the acclimatization period, the animals were accustomed to the environmental conditions of the study and to the diet.

ENVIRONMENTAL CONDITIONS
- Temperature: 22°C ± 3°C
- Humiddity: 30 – 70%
- Photoperiod (hrs dark / hrs light): 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)

IN-LIFE DATES: From: 2012-01-23 To: 2012-02-15
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal and dorso-lateral parts of the trunk
- % coverage: 10 % of the total body surface area
- Type of wrap if used: air-permeable dressing (4 layers of absorbent gauze and stretch bandage)

REMOVAL OF TEST SUBSTANCE
- Washing: rinsing of the application site with warm water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied: 4.5 mL/kg bw
- Concentration: undiluted
- Constant volume or concentration used: constant concentration

VEHICLE
- unchanged (no vehicle)
Duration of exposure:
24 h
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Recording of clinical signs several times on the day of administration, and at least once daily thereafter
each workday for the individual animals. Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of
observation
- Necropsy of survivors performed: yes, incl. gross-pathology examination
- Other examinations performed: scoring of skin findings 30 – 60 minutes after removal of the semi-occlusive dressing (day 1), weekly thereafter and
on the last day of observation, mortality or moribund animals at least once each workday.
Statistics:
Not performed.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
No signs of systemic toxicity or skin effects were observed in the animals. No local findings were observed.
Body weight:
The mean body weight of the animals increased within the normal range throughout the study period with the exception of one female which showed
stagnation of body weight after the first post-exposure week, but gained weight in a normal range during the second week.
Gross pathology:
No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
5 000 mg/kg bw
Quality of whole database:
GLP and guideline study, whole database factor: 1.

Additional information

Oral:

In an acute oral toxicity study (BASF SE, 1989), a group of young adult 5 male and female , fasted Wistar rats were given a single oral dose of Delta-Valerolactone in water at a dose of 2000 mg/kg bw (limit test) and observed for 14 days. No clinical signs, mortality or necropsy findings were noted and no influence on body weight was reported.

 Oral LD50Males =  > 2000 mg/kg bw

      Females = > 2000 mg/kg bw

      Combined =  > 2000 mg/kg  bw

Delta-Valerolactone is of NO NOTICEABLE toxicity based on the LD50in male and female rats.

Inhalation (waiver):

In accordance with column 2 of REACH Annex VIII, the test acute toxicity after inhalation (required in section 8.5) does not need to be conducted as acute toxicity studies for oral and dermal application are available.

Dermal:

In an acute dermal toxicity study (Bioassay, 2012), a group of young adult 5 male and female Wistar rats were dermally exposed to Delta-Valerolactone (100% purity) for 24 hours to 10% of body surface area at a dose of  5000 mg/kg bw (limit test).  Animals then were observed for 14 days. There were no treatment related clinical signs, mortality, necropsy findings or changes in body weight.

 Dermal LD50Males = > 5000 mg/kg bw

     Females =  > 5000 mg/kg bw

      Combined =  > 5000 mg/kg bw

Delta-Valerolactone is of NO NOTICEABLE toxicity based on the LD50 values in male and female rats.


Justification for selection of acute toxicity – oral endpoint
The key study was selected for selection.

Justification for selection of acute toxicity – dermal endpoint
The key study was selected for selection.

Justification for classification or non-classification

Classification for acute toxicity is not warranted according to the criteria of EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No 1272/2008.