Registration Dossier

Administrative data

Endpoint:
acute toxicity: other routes
Type of information:
experimental study
Adequacy of study:
other information
Study period:
From 7 JUNE 1977 to 12 AUG 1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study was carried out prior to GLP and OECD guidelines but was conducted according to acceptable procedures at the time.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977

Materials and methods

Test guideline
Qualifier:
no guideline available
Guideline:
other: The followed procedure is similar to OECD 401/402, however the application is done by intraperitoneal injection
Deviations:
not specified
Principles of method if other than guideline:
Groups of five female rats (Charles River Sprague Dawley - weighing 106-155 g) were dosed with Galaxolide 50 (65% HHCB in DEP) by intraperitoneal injection at different doses and observed for 7 days. This study was conducted prior to GLP and OECD guidelines but was conducted according to acceptable procedure at the time.
GLP compliance:
not specified
Remarks:
This study was prior to GLP and OECD guidelines but was conducted according to acceptable procedures at the time.
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited int he study report): Galaxolide 50
- Date received: 7/15/77
- Physical state: A clear liquid
- Lot/Batch No.: SG-087-2030
- Purity: Assumed 50% active

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
Initial bodyweight 106-155 g

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
unchanged (no vehicle)
Doses:
0.1, 0.215, 1.0 and 4.64 g/kg bw Galaxolide 50, equivalent to 0.065, 0.14, 0.65 and 3.0 g/kg bw HHCB.
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: Immediately after dosing at one, four and 24 hrs and once daily thereafter for at total 7 days.
- Necropsy of survivors performed: yes
Statistics:
Mortality data was analyzed statistically, utilizing the tables of Horn, HJ. Biometrics 12, 311, 1956.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
3 160 mg/kg bw
Remarks on result:
other: The LD50 was 1.58 g/kg BW expressed as HHCB equivalents
Mortality:
4/5 animals treated at the high dose (4.64 g/kg bw Galaxolide 50) were found dead at 24h. The remaining animal treated with this dose was found dead the next day. There were no deaths at the dose of 1.0 g/kg bw.
Clinical signs:
At 1.0 g/kg bw Galaxolide 50, 3 animals were observed to be in a depressed condition within two hours of dosing but returned to normal at 24h. Lethargy and depression were observed in 4/5 animals at 4.64 g/kg bw Galaxolide within 2 hrs. The remaining animal was prostate at 24 hr.
Gross pathology:
Animals found dead exhibited the effects expected at their respective stages of autolysis; all other animals exhibited no remarkable necropsy findings.

Any other information on results incl. tables

Table 1: mortality data       

   Time of death  Time of death  Time of death
 Dose (g/kg) Concentration (%)  Immediate  1 -24 hrs  2 -7 days 
 0.1 100  0/5  0/5  0/5 
 0.215 100  0/5  0/5  0/5 
 1 100 0/5  0/5  0/5 
 4.64 100  0/5  4/5  4/5 
         

Applicant's summary and conclusion

Conclusions:
The acute intraperitioneal toxicity of HHCB is low. There is no need to classify HHCB for acute toxicity.
Executive summary:

Groups of five female rats (Charles River Sprague Dawley – weighing 106-155 g) were dosed with Galaxolide 50 (65% HHCB in DEP) by intraperitoneal injection at doses of 0.1, 0.215, 1.0 or 4.64 g/kg bw, (equivalent to 0.065, 0.14, 0.65 or 3.0 g/kg bw HHCB) and observed for 7 days. At 1.0 g/kg, 3 animals were observed to be in a depressed condition within two hr of dosing but returned to normal at 24 hr. There were no deaths at this dose. Lethargy and depression were observed in 4/5 animals at the high dose within 2 hr and all were found dead at 24 hr. The remaining animal was prostate at 24 hr and found dead the next day. Based on these observations an IP LD50of 3.16 g/kg bw (equivalent to 2.1 g/kg bw HHCB) was calculated. This study was conducted prior to GLP and OECD guidelines but was conducted according to acceptable procedure at the time.