Registration Dossier

Administrative data

Description of key information

Acute oral toxicity

The studies in three species are pre-guideline and pre-GLP studies published in one paper in AMA Archives of Industrial Health. In this publication the acute oral toxicity of the test item was investigated in rat, mouse and rabbit. There the number of animals, the administered dose level and mortality were missing. However, the acute oral LD50 values were calculated with their confidence limits according to the method of Litchfield and Wilcoxon (1948). Despite of decreasing acute oral toxicity (LD50) from mouse (980 mg/kg bw), rabbit (1240 mg/kg bw) to rat (2570 mg/kg bw), the authors (Hine et al. 1958) agreed that there was no noticeable species variation for the test item. In this weight of evidence approach the LD50 value of mouse 980 mg/kg bw was taken as worst case for the hazard assessment of acute oral toxicity.

Acute inhalation toxicity

The published data of Hine et al (1958) showed that 8-hour inhalation exposure of the test item saturated vapors (the maximum attainable concentration) does not resulted any systemic toxicity in rat. In addition, the vapour pressure of the test item at 25 °C is very low: 0.0059 Pa (Envigo2018_TS67LQ_Key). Therefore, it was suggested that test item is not the subject of acute inhalation toxicity classification.

Acute dermal toxicity

The paper of Hine et al (1958) indicated that no toxicity hazard could be associated with percutaneous absorption of the uncured resins (diglycidyl resorcinol). Therefore, it is expected that the test item is not the subject of acute dermal toxicity classification.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
The data for this study was accepted for publication on 01 July 1957
Reliability:
other: The acute toxicity of this compound was assessed as part of a larger study on the toxicity of epoxy resins
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Reason / purpose:
other: Publication
Qualifier:
no guideline available
Principles of method if other than guideline:
Single administration was given to male rats of the Long-Evans strain. The animals were observed for the following 10 days, and those that died were subjected to necropsy. At the end of the observation period, the survivors were killed for necropsy, and sections of their tissues were preserved in 10% formalin for histologic examination. LD50 values were calculated according to the method of Litchfield and Wilcoxon (1948) or the method of Weil (1952). The test item diluted with propylene glycol was given intragastrically to rats.
GLP compliance:
no
Test type:
other: SIngle intragastric adminstration
Limit test:
no
Specific details on test material used for the study:
No data
Species:
rat
Strain:
Long-Evans
Sex:
male
Details on test animals and environmental conditions:
Male rats (110-150 g), Long-Evans strain
Route of administration:
oral: gavage
Vehicle:
propylene glycol
Details on oral exposure:
The test material was given to male rats (110-150 g) as a single Intragastric administration by means of a ball-point needle and syringe - dose level not reported

VEHICLE
- Concentration in vehicle: 10%
- Amount of vehicle (if gavage): not available
- Justification for choice of vehicle: not available
Doses:
No dose level reported
No. of animals per sex per dose:
five or six males
Control animals:
no
Details on study design:
- Duration of observation period following administration: 10 days
- Necropsy of survivors performed: yes, at the end of the observation period the animals were killed and sections of their tissues were preserved in 10% formalin for histologic examination.
- LD50 values were calculated according to the method of Litchfield and Wilcoxon (1948)
- Other examinations performed: clinical signs
Statistics:
LD50 values with their confidence limits were calculated according to the method of Litchfield and Wilcoxon (1948)
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
2 570 mg/kg bw
Based on:
test mat.
95% CL:
2 200 - 3 000
Mortality:
not reported
Clinical signs:
Moderate depression, slight dyspnea. In surviving animals loss of weight and diarrhoea. Animals that died within 48 hours had a blood-tinged nasal discharge.
Body weight:
not reported
Gross pathology:
nonspecific, chief effect of local irritation
Other findings:
none
Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral toxicity test showed an LD50 of 2570 mg/kg
Executive summary:

Acute oral toxicity: In this study, male rats were administered the resorcinol diglycidyl ether. No administered dose, no number of animals, no mortality or body weight details are reported. The acute oral LD50 for the substance in male rats was determined to be 2570 mg/kg

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
The data for this study was accepted for publication on 01 July 1957
Reliability:
other: The acute toxicity of this compound was assessed as part of a larger study on the toxicity of epoxy resins
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Qualifier:
no guideline available
Principles of method if other than guideline:
Single administration was given to male mice of the Webster strain. The animals were observed for the following 10 days, and those that died were subjected to necropsy. At the end of the observation period, the survivors were killed for necropsy, and sections of their tissues were preserved in 10% formalin for histologic examination. LD50 values were calculated according to the method of Litchfield and Wilcoxon (1948). The test item diluted with propylene glycol was given intragastrically to mice.
GLP compliance:
no
Test type:
other: SIngle intragastric adminstration
Limit test:
no
Specific details on test material used for the study:
Diglycidyl resorcinol; no details reported
Species:
mouse
Strain:
other: Webster strain
Sex:
male
Details on test animals and environmental conditions:
Male mice, 16-22g
Route of administration:
oral: gavage
Vehicle:
propylene glycol
Details on oral exposure:
The test material was given to male mice (16 - 22g) as a single Intragastric administration - dose level not reported
Doses:
No dose level reported
No. of animals per sex per dose:
not reported
Control animals:
no
Details on study design:
- Duration of observation period following administration: 10 days
- Necropsy of survivors performed: yes, at the end of the observation period the animals were killed and sections of their tissues were preserved in 10% formalin for histologic examination.
- LD50 values were calculated according to the method of Litchfield and Wilcoxon (1948)
Statistics:
LD50 values and confidence limits were calculated according to the method of Litchfield and Wilcoxon (1948)
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
980 mg/kg bw
Based on:
test mat.
95% CL:
790 - 1 290
Mortality:
not reported
Clinical signs:
Moderate depression, slight dyspnea. In surviving animals loss of weight and diarrhoea. Animals that died within 48 hours had a blood-tinged nasal discharge.
Body weight:
not reported
Gross pathology:
Gross pathology was nonspecific and the chief effect was that of local irritation.
Other findings:
none
Conclusions:
The acute oral toxicity test showed an LD50 of 980 mg/kg
Executive summary:

Acute oral toxicity: In this study, male mice were administered the resorcinol diglycidyl ether. No administered dose, no number of animals, no mortality or body weight details are reported.

The acute oral LD50 for the substance in male mice was determined to be 980 mg/kg

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
The data for this study was accepted for publication on 01 July 1957
Reliability:
other: The acute toxicity of this compound was assessed as part of a larger study on the toxicity of epoxy resins
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Qualifier:
no guideline available
Principles of method if other than guideline:
Single administration was given to male albino rabbits. The animals were observed for the following 10 days, and those that died were subjected to necropsy. At the end of the observation period, the survivors were killed for necropsy, and sections of their tissues were preserved in 10% formalin for histologic examination. LD50 values were calculated according to the method of Litchfield and Wilcoxon (1948). The test item diluted with propylene glycol was given intragastrically to rabbits.
GLP compliance:
no
Test type:
other: SIngle intragastric adminstration
Limit test:
no
Specific details on test material used for the study:
Diglycidyl resorcinol; no details reported
Species:
rabbit
Strain:
other: Albino rabbits
Sex:
male
Details on test animals and environmental conditions:
Male rabbits 2.0 - 3.2 kg
Route of administration:
oral: gavage
Vehicle:
propylene glycol
Details on oral exposure:
The test material was given to male rabbits (2.0 - 3.2 kg) as a single Intragastric administration - dose level not reported
Doses:
No dose level reported
No. of animals per sex per dose:
not reported
Control animals:
no
Details on study design:
- Duration of observation period following administration: 10 days
- Necropsy of survivors performed: yes, at the end of the observation period the animals were killed and sections of their tissues were preserved in 10% formalin for histologic examination.
- LD50 values were calculated according to the method of Litchfield and Wilcoxon (1948)
Statistics:
LD50 values and their confidence limits were calculated according to the method of Litchfield and Wilcoxon (1948)
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
1 240 - 2 490 mg/kg bw
Based on:
test mat.
95% CL:
880 - 2 490
Mortality:
not reported
Clinical signs:
Moderate depression, slight dyspnea. In surviving animals loss of weight and diarrhoea.
Body weight:
not reported
Gross pathology:
Gross pathology was nonspecific and the chief effect was that of local irritation.
Other findings:
none
Conclusions:
The acute oral toxicity test showed an LD50 of 1240 mg/kg
Executive summary:

Acute oral toxicity: In this study, male rabbits were administered the resorcinol diglycidyl ether. No administered dose, no number of animals, no mortality or body weight details are reported.

The acute oral LD50 for the substance in male rabbits was determined to be 1240 mg/kg.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
980 mg/kg bw
Quality of whole database:
The key and supporting studies are a pre-guideline and pre-GLP study published in AMA Archives of Industrial Health. In this publication the acute oral toxicity of the test item was investigated in three species (rat, mouse and rabbit). In the publication, the number of animals, the administered dose level and mortality are missing. However, the LD50 values are calculated with their confidence limits according to the method of Litchfield and Wilcoxon (1948) or the method of Weil (1952).

Acute toxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Qualifier:
no guideline available
Principles of method if other than guideline:
Groups of six rats were exposed to saturated vapors of diclycidyl resorcinol at 30±1 °C within 8 hours, by passage through the liquids in two fritted glass bubblers connected in series in a glass chamber of 19.5 L capacity. The motor-driven syringe assembly delivered measured amounts of the test compound from a 10 mL. Luer-Lok syringe into an evaporator through which metered air moved at a uniform rate. The air flow was set at approximately 3 to 11 L per minute, depending on the concentration desired. Nominal concentrations were calculated by the standard gas-concentration formula of Jacobs and were checked by determining the total quantity of material vaporized.
GLP compliance:
no
Remarks:
pre-GLP
Test type:
other: 8-hour exposure to saturated vapors (the maximum attainable concentration)
Limit test:
yes
Species:
rat
Strain:
Long-Evans
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: commercial laboratory in Gilroy, California
- Weight at study initiation: 110-150 g
- Housing: six to a cage
- Diet: standard laboratory pellets
- Water: tap water
- Acclimation period: for about two weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 14 and 18
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Motor-driven syringe assembly: Luer-Lok syringe into an evaporator through which metered air moved at a uniform rate
- Exposure chamber volume: 19.5 L
- Method of holding animals in test chamber: 6 animals/chamber
- Method of conditioning air: high concentration was obtained by bubling air through a fritted glass disc immersed in the compound, which was held in a glass container
- Source and rate of air: air flow was set at 3 to 11 L/min, depending on the concentration desired
- Temperature, humidity, pressure in air chamber: 30±1 °C
Analytical verification of test atmosphere concentrations:
no
Remarks:
the concentration was too low to permit accuracy of determination
Duration of exposure:
8 h
Concentrations:
saturated vapour of diglycidyl resorcinol
No. of animals per sex per dose:
6 males
Control animals:
no
Details on study design:
- Duration of observation period following administration: 10 days
- Frequency of observations and weighing: noted weighing changes
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, gross pathology
Statistics:
one level tested
Key result
Sex:
male
Dose descriptor:
other:
Remarks:
the maximum attainable concentration
Effect level:
other: the maximum attainable concentration
Based on:
test mat.
Exp. duration:
8 h
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
Not reported
Clinical signs:
other: Not reported
Body weight:
Not reported
Gross pathology:
Not reported
Other findings:
No systemic toxicity has resulted from inhalation of the saturated vapours
Interpretation of results:
other: no toxicity hazard could be associated at the maximum attainable concentration
Conclusions:
The test item diglycidyl resorcinol does not need to be classified as no toxicity hazard could be associated at the maximum attainable concentration.
Executive summary:

The six rat males of the Long-Evans strain (bw 110 -150 g) were exposed with the saturated vapor of diglycidyl resorcinol for eight hours.

The authors concluded that no practical toxicity hazard could be associated.

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Qualifier:
no guideline available
Principles of method if other than guideline:
Groups of six mice were exposed to saturated vapors of diclycidyl resorcinol at 30±1 °C within 8 hours, by passage through the liquids in two fritted glass bubblers connected in series in a glass chamber of 19.5 L capacity. The motor-driven syringe assembly delivered measured amounts of the test compound from a 10 mL. Luer-Lok syringe into an evaporator through which metered air moved at a uniform rate. The air flow was set at approximately 3 to 11 L per minute, depending on the concentration desired. Nominal concentrations were calculated by the standard gas-concentration formula of Jacobs and were checked by determining the total quantity of material vaporized.
GLP compliance:
no
Remarks:
pre-GLP
Test type:
other: 8-hour exposure to saturated vapors (the maximum attainable concentration)
Limit test:
yes
Species:
mouse
Strain:
other: Webster
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: commercial laboratory in Gilroy, California
- Weight at study initiation: 16-22 g
- Housing: six to a cage
- Diet: standard laboratory pellets
- Water: tap water
- Acclimation period: for about two weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 14 and 18
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Motor-driven syringe assembly: Luer-Lok syringe into an evaporator through which metered air moved at a uniform rate
- Exposure chamber volume: 19.5 L
- Method of holding animals in test chamber: 6 animals/chamber
- Method of conditioning air: high concentration was obtained by bubbling air through a fritted glass disc immersed in the compound, which was held in a glass container
- Source and rate of air: air flow was set at 3 to 11 L/min, depending on the concentration desired
- Temperature, humidity, pressure in air chamber: 30±1 °C
Analytical verification of test atmosphere concentrations:
no
Remarks:
the concentration was too low to permit accuracy of determination
Duration of exposure:
8 h
Concentrations:
saturated vapour of diglycidyl resorcinol
No. of animals per sex per dose:
6 males
Control animals:
no
Details on study design:
- Duration of observation period following administration: 10 days
- Frequency of observations and weighing: noted weighing changes
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, gross pathology
Statistics:
one level tested
Sex:
male
Dose descriptor:
other:
Remarks:
the maximum attainable concentration
Effect level:
other: the maximum attainable concentration
Based on:
test mat.
Exp. duration:
8 h
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
Not reported
Clinical signs:
other: Not reported
Body weight:
Not reported
Gross pathology:
Not reported
Other findings:
No systemic toxicity has resulted from inhalation of the saturated vapours
Interpretation of results:
other: no toxicity hazard could be associated at the maximum attainable concentration
Conclusions:
The test item diglycidyl resorcinol does not need to be classified as no toxicity hazard could be associated at the maximum attainable concentration.
Executive summary:

The six mice males of the Webster strain (bw 16 -22 g) were exposed with the saturated vapor of diglycidyl resorcinol for eight hours.

The authors concluded that no practical toxicity hazard could be associated.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The published paper is pre-GLP and pre-guideline document with the reference to the test methods in the previous publications (Hine et al 1953 and Hine et al 1953). The information that 8-hour saturated vapour (the maximum attainable concentration) exposure with the test item does not resulted any systemic toxicity in rats and mice, may suggest that compound is not needed to be classified.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Justification for type of information:
The paper of Hine et al (1958) indicated that no toxicity hazard could be associated with percutaneous absorption of the uncured resins (diglycidyl resorcinol). Therefore, it is expected that the test item is not the subject of acute dermal toxicity classification.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The published paper is pre-GLP and pre-guideline document. There no number of exposed animals or study design is available.

Additional information

Based on the literature data (Hine et al. 1958), it was shown that the test item is more toxic when administered intraperitoneally than when administered intragastrically.

Justification for classification or non-classification

The LD50 value for Acute Oral toxicity is set at 980 mg/kg bw. According to the CLP criteria substances which have an LD50 value within the range 300 < ATE ≤ 2000 is classified as Category 4. H302 -Harmful if swallowed.

Based on the available literature data available for toxicity via the inhalation route to the test item does not result in any systemic toxicity in rats and mice during the 8-hour saturated vapour phase. Therefore it can be concluded the test item is not classified for acute inhation toxicity.