Registration Dossier

Administrative data

Description of key information

Oral LD50 > 5050 mg/kg bw
Inhalation LD50 > 2.51 mg/l
Dermal LD50 > 5050 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:
From November 21, 2001 to January 02, 2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test conducted following internationally accepted testing guidelines and performed according to the GLP.
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
protocol devation from 5 males and 5 females did not affect quality or outcome of study
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Specie & strain: Albino rat; Sprague-Dawley.
- Justification of Species: the rat is a rapresentative rodent species preferred by various regulatory agencies for use in an acute oral study.
- Source: Texas Animal Specialities, Humble, TX.
- Age at study initiation: 51 days males and 22 days.
- Weight at study initiation: males: 181 - 326 g; females: 199-218 g.
- Housing: 1 per cage.
- Cage type: suspended, wire bottom, stainless steel.
- Diet: PMI Feeds Inc.TM Formulab #5008; available ad libitum except for approximately 16 hours before dosing.
- Water: municipal water supply analyzed by TNRCC Water Utilities Division; available ad libitum from automatic water system.
- Quarantine period: 5 days.

ENVIRONMENTAL CONDITIONS
Set to maintain
- Temperature: 22 ± 3 °C.
- Humidity: 30 - 70 %.
- Air changes: 10-12 air change/hour.
- Photoperiod: 12 hours light/dark cycle.

IN-LIFE DATES
Animlas born in October 01 and 15, 2001. They were received by the laboratory at November 21 and December 06 and were treated with the test substance on December 19. The in-life portion of the study was termined on January 02, 2002.

No contaminants were expected to have been present in the feed or water which would have interfered with or affected the results of the study.
Route of administration:
oral: gavage
Vehicle:
other: citric acid
Details on oral exposure:
TEST SUBSTANCE PREPARATION and ADMINISTRATION
The test substance was mixed with citric acid to produce a 40 % w/v concentration.

An individual dose was calculated for each animal based on its fasted body weight and administered by gavage at a volume of 12.6 ml/kg.
Each dose was administered using an appropriately sized singe and stainless steel ball-tipped intubation needle. The animals were returned to their cages immediately after dosing.
Doses:
5050 mg/kg (12.6 ml/kg).
No. of animals per sex per dose:
6 males and 4 females (nulliparous and non-pregnant) for a single fixed dose.
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations for mortality and clinical/behavioral signs of toxicity were made at least three times on the day of dosing (Day 0) and at least once daily thereafter for 14 days. Individual body weights were recorded just prior to dosing and on Days 7 and 14.
- Necropsy of survivors performed: yes; on Day 14 after dosing, each animal was euthanized by an overdose of CO2. All study animals were subjected to gross necropsy and all abnormalities were recorded.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 050 mg/kg bw
Based on:
test mat.
Mortality:
There was no mortality during the study. The estimated acute oral LD50, as indicated by the data, was determined to be greater than 5050 mg/kg.
Clinical signs:
Clinical signs included activity decrease, piloerection and respiratory chirp in both sexes, and diarrhea and sensitivity to touch in males.
Animals were asymptomatic by Day 1.
Body weight:
Body weight gain was unaffected by the administration of the test substance.
Gross pathology:
The gross necropsy conducted at termination of the study revealed no observable abnormalities.

Reactions and Severity Time after Treatment  
hours days
MALES 1 2 4 1 2 3 4 5 6 7 8 9 10 11 12 13 14
Activity decrease 6 6 5 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Sensitive to touch 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Diarrhea 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Piloerection 0 6 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Respiratory chirp 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0
FEMALES  
Respiratory chirp 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Activity decrease 4 4 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Piloerection 0 4 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Interpretation of results:
not classified
Remarks:
Migrated information according to the CLP Regulation Criteria used for interpretation of results: EU
Conclusions:
LD50 is greater than 5050 mg/kg bw in males and females
Executive summary:

The test substance was evaluated for its acute oral toxicity potential in albino rats when administered as a single gavage dose at a level of 5050 mg/kg bw to males and females. No mortality occurred during the study. Clinical signs included activity decrease, diarrhea, piloerection, respiratory chirp and sensitivity to touch, which were no longer evident by Day 1. There was no effect on body weight gain. The gross necropsy conducted at termination of the study revealed no observable abnormalities.

Conclusion

The acute oral LD50 was determined to be greater than 5050 mg/kg bw

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 050 mg/kg bw

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:
From November 21 to December 14, 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test conducted following internationally accepted testing guidelines and performed according to the GLP.
Qualifier:
according to
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Justification of Species: the rat is a representative rodent species preferred by various regulatory agencies for use in an acute inhalation studies.
- Source: Texas Animal Specialities, Humble, TX.
- Age at study initiation: 51 days.
- Weight at study initiation: males: 250-277 g; females: 182-195 g.
- Housing: one per cage.
- Cage type: suspended, wire bottom, stainless steel.
- Diet: PMI TM Lab Diet Formula #5008; available ad libitum except during the exposure period.
- Water: municipal water supply analyzed by TNRCC Water Utilities Division; from automatic water system, available ad libitum except during the exposure period.
- Quarantine period: 5 days.

ENVIRONMENTAL CONDITIONS
Set to maintain
- Temperature: 22 ± 3 °C.
- Humidity: 30 - 70 %.
- Air changes: 10-12 air change/hour.
- Photoperiod: 12 hours light/dark cycle.

IN-LIFE DATES
Animlas born in October 01, 2001. They were received by the laboratory at November 21 and were treated with the test substance on November 30. The in-life portion of the study was termined on December 14, 2001.

No contaminants were expected to have been present in the feed or water which would have interfered with or affected the results of the study.
Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
PRESTUDY TESTING
Trial assays were conducted to determine which method(s) of aerosolizing the test substance into the exposure chamber would produce an acceptable concentration and mass median aerodynamic diameter (MMAD).

EXPOSURE CHAMBER
A 500 l nose-only stainless steel, dynamic flow inhalation chamber was utilized in this experiment. The body of the chamber has 25 ports in 5 rows. Polycarbonate tubes are inserted into 10 designated individual ports. The test substance is introduced through the opening in the top of the chamber. The bottom section has a corresponding air outlet and a drain valve for cleaning the chamber. The individual polycarbonate tubes are tapered at one end to fit the shape of the animal's head and the back portion is sealed with a rubber cap. The tubes containing the animals fit tightly into the ports, and are sealed with "O" rings.

GENERATION OF TEST ETMOSPHERE
The aerosol was generated by a Gem T Trost Air Mill which aspirated the test substance from a motorized revolving disc delivery system coupled to the mill, then sprayed the resulting aerosol directly into the exposure chamber. Air flow into the chamber was maintained through the use of a calibrated orifice plate at a rate of 22.4 air changes per hour. Air flow was recorded at 30 minute intervals during the exposure period, and was sufficient to ensure an oxygen content of at least 19 % of the exposure atmosphere.
Temperature and humidity were recorded at 30 minute intervals during the exposure period from a Taylor wet bulb/dry bulb hygrometer located in the exposure chamber.

TEST SUBSTANCE ADMINISTRATION
Healthy albino rats were released from quarantine, and five males and five females were selected for testing. The test substance was ground for 24 hours and sifted prior to exposure. The animals were exposed to an aerosol generated from the undiluted test substance (fine powder) for a period of four hours. When 99 % concentration (t-99) was attained, the animals which were individually housed in polycarbonate exposure tubes were inserted into a 500 l stainless steel nose-only inhalation chamber for the specified exposure period. At the termination of the exposure period, the animals were returned to their stock laboratory cages.

DETERMINATION OF CONCENTRATION
The concentration of test substance in the exposure atmosphere (taken from the breathing zone of the animals) was determined gravimetrically twice per hour and nominally at the end of the exposure. The gravimetric concentration was determined by passing a known volume of exposure air through a pre-weighed filter and dividing the amount of test substance deposited on the filter by the volume of air which passed through the filter. The nominal concentration was determined by dividing the loss in weight of the test substance after the exposure by the total volume of air which passed through the chamber.

PARTICLE SIZE DISTRIBUTION
Particle size, taken from the breathing zone of the animals, was determined twice during the exposure, using a cascade impactor, at a rate of 7.1 l/minute for a duration of 20 seconds. The MMAD and particle size distributions are calculated from these data by a computer program utilizing probit analysis.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
Determined gravimetrically twice per hour and nominally at the end of the exposure.
Duration of exposure:
ca. 4 h
Concentrations:
2.51 mg/l, with an average MMAD of 2.0 µm.
No. of animals per sex per dose:
5 males and 5 females (nulliparous and non-pregnant) x dose
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation for mortality and signs of pharmacologic and/or toxicological effects were made frequently an the day of exposure and at least once daily thereafter for 14 days (Day 0 is day of exposure). Individual body weights were recorded just prior to the inhalation exposure and on Days 7 and 14.
- Necropsy of survivors performed: yes. On Day 14 after exposure, each animal was euthanized by an intraperitoneal injection of Fatal Plus@ (Vortech Pharmaceuticals, Dearbom, MI 48126). All study animals were subjected to gross necropsy, and all abnormalities were recorded.
Statistics:
In order to calculate a mean exposure, the Mean Value Theorem of Calculus was used to properly weight the concentration, since the concentrations could not be measured continuously. This method weights concentrations based on the time span of each concentration. A concentration can be calculated for each minute, which better represents the exposure concentration received by each animal.
Preliminary study:
Trial assays were conducted to determine which method(s) of aerosolizing the test substance into the exposure chamber would produce an acceptable concentration and mass median aerodynamic diameter (MMAD).
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 2.51 mg/L air (nominal)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
There was no mortality during the study. As indicated by the data, the acute inhalation LC50 for Lysozyme Technical is greater than 2.51 mg/l.
Clinical signs:
other: Prominent in-life observations included activity decrease and pilo-erection in both sexes on the day of dosing, and decreased defecation in one female on Day 2.
Body weight:
Body weight gain was unaffected by the administration of the test substance.
Gross pathology:
The gross necropsy conducted on each animal at termination of the study revealed no observable abnormalities.

Reaction and severity

Time after exposure begins

Hours Days
0.5 1.0 2.5 4.5 6.0 1 2 3 4 5 6 7 8 9 10 11 12 13 14
MALES
Pilo-erection (v-s) 0 0 0 5 5 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Activity decrease (v-s) 0 0 0 5 5 0 0 0 0 0 0 0 0 0 0 0 0 0 0
FEMALES
Pilo-erection (v-s) 0 0 0 5 5 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Activity decrease (v-s) 0 0 0 5 5 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Decrease defection 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0
Interpretation of results:
other: not assessable, according to the CLP Regulation
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
LC50 is greater than 2.51 mg/l in males and females
Executive summary:

The test substance was evaluated for its acute inhalation toxicity potential in albino rats. Five males and five females were exposed for four hours to an aerosol generated from the undiluted test substance (fine powder) at a level of 2.51 mg/l.

There was no mortality during the study. Clinical signs included activity decrease and pilo-erection on the day of dosing, and decreased defecation on Day 2. Body weights were unaffected by exposure. The gross necropsy revealed no observable abnormalities.

Conclusion

The acute inhalation LC50 is greater than 2.51 mg/l

According to the CLP Regulation (EC 1272/2008), the higher classification threshold limit for acute inhalation toxicity is fixed at 5 mg/l for dust and mist, thus the test result can be used only in order to exclude a classification as toxic if inhaled (category 3: 0.5 < ATE ≤ 1.0).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
2 510 mg/m³

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:
From November 28 to December 20, 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test conducted following internationally accepted testing guidelines and performed according to the GLP.
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Specie & strain: Albino rabbit; New Zealand White.
- Justification of Species: the rabbit is a representative species preferred by various regulatory agencies for use in an acute dermal testing.
- Source: Ray Nichols Rabbitry; Lumberton, TX
- Age at study initiation: 80 days.
- Weight at study initiation: males: 2.300-2.700 kg; females: 2.025-2.525 kg.
- Housing: one per cage.
- Cage type: suspended, wire bottom, stainless steel.
- Diet: PMI Feeds, Inc.TM Lab Rabbit Diet #5321, in measured amounts.
- Water: municipal water supply analyzed by TNRCC Water Utilities Division; tap water, available ad libitum (automatic system).
- Quarantine period: 5 days.

ENVIRONMENTAL CONDITIONS
Set to maintain
- Temperature: 20 ± 3 °C
- Humidity: 30 - 70 %
- Air changes: 10-12 air change/hour.
- Photoperiod: 12 hours light/dark cycle.

IN-LIFE DATES
Animlas born in September 09, 2001. They were received by the laboratory at November 28 and were treated with the test substance on December 06. The in-life portion of the study was termined on December 20, 2001.

No contaminants were expected to have been present in the feed or water which would have interfered with or affected the results of the study.
Type of coverage:
occlusive
Vehicle:
water
Remarks:
deionised
Details on dermal exposure:
TEST SITE and APPLICATION of TS
- Preparation: each animal was prepared on the day prior to treatment by clipping the dorsal surface of the trunk free of hair. Care was taken to avoid abrading the skin. Only those animals with exposure area free of pre-existing skin irritation or defects were used for the study.
- Test substance application: the test substance was applied evenly to each exposure area in a thin, uniform layer.
- % coverage: expose not less than 10 %.
- Type of wrap if used: the area of application was covered with 4 ply, 8 x 4 in. surgical gauze patch and secured with non-irritating adhesive tape. The trunk of each animal was then wrapped with orthopaedic stockinet which was secured in place with non-irritating adhesive tape to prevent possible ingestion of the test substance.

REMOVAL OF TEST SUBSTANCE
- Washing: washed with room temperature tap water and a clean cloth.
- Time after start of exposure: after 24 hours.

VEHICLE
- Amount(s) applied: each dose was moistened with sufficient amount of deionised water (0.96 ml/g of test substance).
Duration of exposure:
24 hours
Doses:
5050 mg/kg
No. of animals per sex per dose:
5 males and 5 females (nulliparous and non-pregnant)
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations for mortality and clinical/behavioural signs of toxicity were made at least three times on the day of dosing (Day 0) and at least once daily thereafter for 14 days. Individual body weights were recorded just prior to dosing and on Days 7 and 14.
- Necropsy of survivors performed: yes; on Day 14 after dosing, animals were euthanized by an intracardiac injection of Fatal Plus®. All study animals were subjected to gross necropsy and all abnormalities were recorded. After necropsy, the animal carcasses were discarded.
- Other examinations performed: observations for evidence of dermal irritation were made at approximately 60 minutes after removal of wrappings, and on Days 4, 7, 11 and 14.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 050 mg/kg bw
Based on:
test mat.
Mortality:
There was no mortality during the study. The estimated acute dermal LD50, as indicated by the data, was determined to be greater than 5050 mg/kg body weight.
Clinical signs:
Prominent in-life observations included decreased defecation and soft faeces in both sexes, on the day of dosing and Day 12.
Body weight:
Body weight gain was unaffected by the administration of the test substance.
Gross pathology:
The gross necropsy conducted at termination of the study revealed no observable abnormalities, except for pale kidneys in two males.
Other findings:
DERMAL IRRITATION
Irritation included very slight erythema through Day 4, very slight oedema an Day 1, and desquamation an Days 7 and 11; test substance residue was also observed.

Pharmacologic and/or toxicological signs

Reaction and severity Time after treatment
Hours Days
1.0 2.0 4.0 1 2 3 4 5 6 7 8 9 10 11 12 13 14
MALES
Soft faeces 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Decreased defecation 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3 0 0
FEMALES
Decreased defecation 1 0 0 0 0 0 0 0 0 0 0 0 0 0 3 0 0
Soft faeces 0 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0

Signs of dermal irritation

Animal Day 1 Day 4 Day 7 Day 11 Day 14
Er Oed Other Er Oed Other Er Oed Other Er Oed Other Er Oed Other
Male 1 0 T 0 0 T 0 0 - 0 0 - 0 0 -
Male 1 0 T 1 0 T 0 0 - 0 0 - 0 0 -
Male 1 1 T 0 0 T 0 0 - 0 0 - 0 0 -
Male 1 1 T 0 0 T 0 0 D, T 0 0 D, T 0 0 T
Male 1 0 T 0 0 T 0 0 D, T 0 0 - 0 0 -
Female 1 0 T 0 0 T 0 0 - 0 0 - 0 0 -
Female 1 0 T 0 0 T 0 0 T 0 0 - 0 0 -
Female 1 1 T 0 0 T 0 - 0 0 - 0 -
Female 1 0 T 1 0 T 0 0 D, T 0 0 D, T 0 0 -
Female 1 0 T 0 0 T 0 0 T 0 0 D, T 0 0 -

Er = Erythema; 0 = None; 1 = Very slight; 2 = Well-defined; 3 = Moderate; 4 = Severe

Oed = Oedema; 0 = None; 1 = Very slight; 2 = Slight; 3 = Moderate; 4 = Severe

D = Desquamation; T = Test substance residue

Note: A dash (-) is used if no other irritation is observed

Interpretation of results:
not classified
Remarks:
Migrated information according to the CLP Regulation Criteria used for interpretation of results: EU
Conclusions:
LD50 is greater than 5050 mg/kg in males and females.
Executive summary:

The test substance was evaluated for its dermal toxicity potential and relative skin irritancy when a single dose moistened with 0.96 ml of deionised water/g test substance, at a level of 5050 mg/kg, was applied to the intact skin of albino rabbits.

No mortality occurred during the study. Clinical signs included decreased defecation and soft faeces on Days 0 and 12 of the study. Signs of dermal irritation included erythema, oedema and desquamation. There was no effect on body weight gain during the study. The gross necropsy conducted at termination of the study revealed no observable abnormalities, except for pale kidneys in two animals.

Conclusion

The estimated LD50 was determined to be greater than 5050 mg/kg

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 050 mg/kg bw

Additional information

ACUTE TOXICITY - ORAL ROUTE

A GLP study is available; it was performed on the lysozyme hydrochloride and following the EPA OPPTS 870.1100 testing guideline. The test substance was evaluated for the acute oral toxicity potential in albino rats, administering a single gavage dose at a level of 5050 mg/kg bw to both males and females. No mortality occurred during the study. Clinical signs included activity decrease, diarrhea, piloerection, respiratory chirp and sensitivity to touch, which were no longer evident by Day 1. There was no effect on body weight gain. The gross necropsy conducted at termination of the study revealed no observable abnormalities.

Literature sources reported that lysozyme was tolerated orally at up to 4000 mg/kg bw in mice and rats (Bianchi, 1982). Further oral acute toxicity data are available from a lysozyme monograph (Barbara and Pellegrini, 1976): the lethal dose 50 was reported as greater than 13000 mg/kg both in mice and guinea pigs and greater than 15000 mg/kg in rats, showing that lysozyme was well tolerated up to high doses in these species. In dogs, the lethal dose 50 was stated as greater than 10000 mg/kg; no influence on body temperature, heart and respiration rate were reported and no signs of gastric intolerance were observed.

ACUTE TOXICITY - INHALATION ROUTE

According to the REACH Regulation, Annex VIII, Column 2 (specific rules for adaptation from column 1), in addition to the oral route (8.5.1), for substances other than gases, the information mentioned under 8.5.2 to 8.5.3 shall be provided for at least one other route. The choice for the second route will depend on the nature of the substance and the likely route of human exposure. Because of the physical state and the trade forms of the substance, the inhalation can be considered as not an appropriate route of exposure; lysozyme HCl is primarily marketed/used both as granular and liquid form, depending to the final application.

Nevertheless, a study by the inhalation route is available. The test substance was evaluated for the acute inhalation toxicity potential in albino rats. Five males and five females were exposed for four hours to an aerosol generated from the undiluted test substance (fine powder) at a level of 2.51 mg/l. There was no mortality during the study. Clinical signs included activity decrease and pilo-erection on the day of dosing, and decreased defecation on Day 2. Body weights were unaffected by exposure. The gross necropsy revealed no observable abnormalities.

The test material resulted not toxic at a nominal concentration of 2.51 mg/l, however the results of the study is not assessable under the CLP Regulation (EC 1272/2008) criteria.

ACUTE TOXICITY - DERMAL ROUTE

The lysozyme hydrochloride was evaluated for its dermal toxicity potential and relative skin irritancy when a single dose moistened with 0.96 ml of deionised water/g test substance, at a level of 5050 mg/kg, was applied to the intact skin of albino rabbits. No mortality occurred during the study. Clinical signs included decreased defecation and soft faeces on Days 0 and 12 of the study. Signs of dermal irritation included erythema, oedema and desquamation. There was no effect on body weight gain during the study. The gross necropsy conducted at termination of the study revealed no observable abnormalities, except for pale kidneys in two animals.

REFERENCE

Barbara L. and Pellegrini R. (1976). Fleming's Lysozyme. Edizioni Minerva Medica, pp.58-65.

Bianchi C (1982). Antigenic properties of hen egg white lysozyme (Fleming's lysozyme) and notes on its acute/sub-acute toxicity. Curr. Therap. Res., 31: 494-505.


Justification for selection of acute toxicity – oral endpoint
Test conducted according to internationally accepted testing guidelines.

Justification for selection of acute toxicity – inhalation endpoint
Test conducted according to internationally accepted testing guidelines.

Justification for selection of acute toxicity – dermal endpoint
Test conducted according to internationally accepted testing guidelines.

Justification for classification or non-classification

According to the CLP Regulation (EC 1272/2008), 3.1 Acute toxicity section, substances can be allocated to one of four toxicity categories based on acute toxicity by the oral, dermal or inhalation route according to the numeric criteria. Acute toxicity values are expressed as (approximate) LD50 (oral, dermal) or LC50 (inhalation) values or as acute toxicity estimates (ATE).

The oral LD50 value was established to be greater than 5050 mg/kg body weight, therefore the test substance is out of any classification limit for acute oral toxicity (oral acute toxicity category 4: 300 < ATE ≤ 2000 mg/kg bw).

The inhalation LD50 value was established to be greater than 2.51 mg/l. The higher classification threshold limit for acute inhalation toxicity is fixed at 5 mg/l for dust and mist, thus the test result can be used only in order to exclude a classification as toxic if inhaled (category 3: 0.5 < ATE ≤ 1.0).

The dermal LD50 value was established to be higher than 5050 mg/kg body weight, which exceeded the highest CLP limit for classification (dermal acute toxicity category 4: 1000 < ATE ≤ 2000 mg/kg bw).

In conclusion, the test substance is non classified for oral/dermal acute toxicity, according to the CLP Regulation (EC 1272/2008).