Registration Dossier

Diss Factsheets

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified reliable without restriction. The study was conducted in accordance with OECD Guideline 401 Recommendations and followed GLP.
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in Section 13.
Cross-reference
Reason / purpose for cross-reference:
read-across: supporting information
Reference
Endpoint:
acute toxicity: oral
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified reliable without restriction. The study was conducted in accordance with OECD Guideline 401 Recommendations and followed GLP.
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in Section 13.
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hoechst, AG, SPF - Zucht
- Age at study initiation: Male: 7 weeks; Female: 8 weeks
- Weight at study initiation: Male: 175-183 grams; Female: 165-171 grams
- Fasting period before study: 16 hours prior to and 3-4 hours post dosing
- Housing: in fully air-conditioned rooms in makrolonkafigen (type 4) on soft wood pellets in groups of 5
- Diet (e.g. ad libitum): Rat diet Altromin 1324, Altromin GmbH, Lage/Lippe ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: Not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3˚C
- Humidity (%): 55 ± 20%
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light

IN-LIFE DATES: From: 1992-03-04 To: 1992-03-18
Route of administration:
oral: gavage
Vehicle:
other: Sesamol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20% w/v
- Amount of vehicle (if gavage): 10 mL
- Justification for choice of vehicle: Not reported

MAXIMUM DOSE VOLUME APPLIED: 10 mL
Doses:
Single dose of 2000 mg/kg bw
No. of animals per sex per dose:
5/sex
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:observations conducted twice daily and once daily on public holiday. Body weight determinations conducted weekly.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Based on absence of mortality and lack of adverse treatment-related clinical effects observed in male and female rats.
Mortality:
No mortality was observed through the 14-day study period in male or female rats.
Clinical signs:
other: The following clinical signs were observed in the study: crouching position; retracted flanks reduced; unregulated breathing and uncoordinated input; and diarrhea. The symptoms were reversible.
Gross pathology:
Gross necroscopy at termination did not reveal any remarkabale findings.
Interpretation of results:
other: Not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Based on the absence of test material related mortality and lack of adverse signs of clinical toxicity, the acute oral LD50 for Alresat KM 140 (Resin acids and Rosin acids, fumarated, esters with glycerol) is considered to be >2000 mg/kg body weight in the rat.
Executive summary:

In an acute oral toxicity study (Hoechst Pharma Entwicklung Toxikologie, 1992; Klimisch score = 1), 2000 mg/kg bw (200 mL/kg) of Alresat KM 140 (Resin acids and Rosin acids, fumarated, esters with glycerol) in Sesamol was orally administered via gavage to Sprague-Dawley rats (5/sex). The animals were observed over a period of 14 days for mortality and signs of clinical toxicity.

No mortality was observed in male or female rats during the study. The following clinical signs were observed in the study: crouching position; retracted flanks reduced; unregulated breathing and uncoordinated input; and diarrhea. All symptoms were observed to be reversible and the test animals did not exhibit any signs of adverse clinical toxicity. Body weights remained unaffected through the test period and gross necropsy at termination did not reveal any remarkable findings.

Based on the absence of test material related mortality and lack of adverse signs of clinical toxicity, the acute oral LD50 for Alresat KM 140 (Resin acids and Rosin acids, fumarated, esters with glycerol) was considered to be >2000 mg/kg body weight in the rat.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report date:
1992

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
Resin acids and Rosin acids, fumarated, esters with glycerol
EC Number:
307-051-0
EC Name:
Resin acids and Rosin acids, fumarated, esters with glycerol
Cas Number:
97489-11-7
Test material form:
other: solid
Details on test material:
- Name of test material (as cited in study report): Alresat KM 140
- Substance type: Kolofoniumharz modified with fumaric acid and glycerol
- Physical state: Solid, brownish scales
- Lot/batch No.: MAGN 205
- Stability under test conditions: Stable till October 1992
- Storage condition of test material: In the dark at room temperature

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hoechst, AG, SPF - Zucht
- Age at study initiation: Male: 7 weeks; Female: 8 weeks
- Weight at study initiation: Male: 175-183 grams; Female: 165-171 grams
- Fasting period before study: 16 hours prior to and 3-4 hours post dosing
- Housing: in fully air-conditioned rooms in makrolonkafigen (type 4) on soft wood pellets in groups of 5
- Diet (e.g. ad libitum): Rat diet Altromin 1324, Altromin GmbH, Lage/Lippe ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: Not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3˚C
- Humidity (%): 55 ± 20%
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light

IN-LIFE DATES: From: 1992-03-04 To: 1992-03-18

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Sesamol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20% w/v
- Amount of vehicle (if gavage): 10 mL
- Justification for choice of vehicle: Not reported

MAXIMUM DOSE VOLUME APPLIED: 10 mL
Doses:
Single dose of 2000 mg/kg bw
No. of animals per sex per dose:
5/sex
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:observations conducted twice daily and once daily on public holiday. Body weight determinations conducted weekly.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Based on absence of mortality and lack of adverse treatment-related clinical effects observed in male and female rats.
Mortality:
No mortality was observed through the 14-day study period in male or female rats.
Clinical signs:
other: The following clinical signs were observed in the study: crouching position; retracted flanks reduced; unregulated breathing and uncoordinated input; and diarrhea. The symptoms were reversible.
Gross pathology:
Gross necroscopy at termination did not reveal any remarkabale findings.

Applicant's summary and conclusion

Interpretation of results:
other: Not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Based on the absence of test material related mortality and lack of adverse signs of clinical toxicity, the acute oral LD50 for Alresat KM 140 (Resin acids and Rosin acids, fumarated, esters with glycerol) is considered to be >2000 mg/kg body weight in the rat.
Executive summary:

In an acute oral toxicity study (Hoechst Pharma Entwicklung Toxikologie, 1992; Klimisch score = 1), 2000 mg/kg bw (200 mL/kg) of Alresat KM 140 (Resin acids and Rosin acids, fumarated, esters with glycerol) in Sesamol was orally administered via gavage to Sprague-Dawley rats (5/sex). The animals were observed over a period of 14 days for mortality and signs of clinical toxicity.

No mortality was observed in male or female rats during the study. The following clinical signs were observed in the study: crouching position; retracted flanks reduced; unregulated breathing and uncoordinated input; and diarrhea. All symptoms were observed to be reversible and the test animals did not exhibit any signs of adverse clinical toxicity. Body weights remained unaffected through the test period and gross necropsy at termination did not reveal any remarkable findings.

Based on the absence of test material related mortality and lack of adverse signs of clinical toxicity, the acute oral LD50 for Alresat KM 140 (Resin acids and Rosin acids, fumarated, esters with glycerol) was considered to be >2000 mg/kg body weight in the rat.