Registration Dossier

Administrative data

Description of key information

Three acute inhalation, an acute dermal and an acute oral lethality study have been conducted on CAS# 756-12-7.

The results of the studies were:

Oral:

The acute oral LD50 was found to be greater than 2,000 mg/kg body weight when tested according to OECD 425.

Inhalation:

Key Study: The acute 4-hour inhalation LC50 was found to be greater than 148 but less than 213 mg/L (vapor) when tested according to OECD 403.

4-Hour LC50:  > 10000 ppm

4-Hour LC50:   20000 ppm

Dermal:

The acute dermal LD50 was found to be greater than 2,000 mg/kg body weight when tested according to OECD 403.


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:
2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Version / remarks:
2008
Deviations:
no
Remarks:
No deviations occurred that impacted the results of the study.
GLP compliance:
yes
Test type:
up-and-down procedure
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 3M Company, Lot 1
- Expiration date of the lot/batch: 05 June, 2019
- Purity test date: 05 June, 2017

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature.
- Stability under test conditions: Stable

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: None, dosed neat.
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: 11-12 weeks old.
- Weight at study initiation: 186-215 grams
- Fasting period before study: Yes, maximum 20 hours
- Housing: On arrival and following assignment to the study, animals were group housed (up to 5 animals of the same sex and same dosing group together) in polycarbonate cages (Makrolon MIV type; height 18 cm.) containing sterilized sawdust as bedding material (Lignocel S 8-15,
JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) equipped with water bottles. These housing conditions were maintained unless deemed inappropriate by the Study Director and/or Clinical Veterinarian. The room(s) in which the animals were kept were documented in the study records. Animals were separated during designated procedures/activities. Each cage was clearly labeled.
- Diet (e.g. ad libitum): Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany) was provided ad libitum throughout the study, except during designated procedures. The feed was analyzed by the supplier for nutritional components and environmentalcontaminants.
- Water (e.g. ad libitum): Municipal tap-water was freely available to each animal via water bottles. Periodic analysis of the water was performed, and results of these analyses are on file at the Test Facility.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24 C
- Humidity (%): 40-70
- Air changes (per hr): At least 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 10 October, 2017 To: 31 October, 2017
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE: None, dosed neat.

MAXIMUM DOSE VOLUME APPLIED: No data
Doses:
2,000 mg/kg
No. of animals per sex per dose:
5 female
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Postdose observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter. The observation period was 14 days. All the animals were examined for reaction to dosing. The onset, intensity and duration of these signs was recorded (if appropriate). Signs were graded for severity and the maximum grade was predefined at 3 or 4. Grades were coded as slight (grade 1), moderate (grade 2), severe (grade 3) and very severe (grade 4). For certain signs, only its presence (grade 1) or absence (grade 0) was scored. Animals were weighed individually on Day 1 (predose), 8 and 15. A fasted weight was recorded on the day of dosing. Terminal body weights were collected from animals found dead or euthanized moribund after Day 1.
- Necropsy of survivors performed: Yes
- Other examinations performed: clinical signs, body weights, macroscopic examination upon necropsy
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
One animal was found dead on Day 2, no further mortality occurred.
Clinical signs:
Hunched posture, uncoordinated movements and/or piloerection were noted on Day 1 for the animals. In addition, lethargy was noted for the animal that was found dead.
Body weight:
The incidence of reduced body weight gain or slight body weight loss between Days 8 and 15 in several animals were considered not indicative of toxicity, based on the absence of any corroborative findings in these animals.
Gross pathology:
No test item-related abnormalities were found at macroscopic post mortem examination of the animals. In the animal found dead, cannibalism of the abdominal region was noted at macroscopic post mortem examination. In one surviving animal ectopic splenic tissue was noted at macroscopic post mortem examination. This finding is occasionally seen in rats of this age and strain and was therefore considered not toxicologically significant.
Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
Based on the results of the study, the acute oral LD50 value of the test article is greater than 2,000 mg/kg.
Executive summary:

The acute oral lethality potential of the test article was evaluated in female Wistar rats. The study was conducted according to OECD 425 (2008) and was performed in compliance with OECD GLP regulations. The test article was administered neat via oral gavage to a single rat at 2,000 mg/kg body weight for the pilot test. Subsequently, four additional female rats were dosed at 2,000 mg/kg body weight. Postdose observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter. The observation period was 14 days. All the animals were examined for reaction to dosing. The onset, intensity and duration of these signs was recorded (if appropriate). Signs were graded for severity and the maximum grade was predefined at 3 or 4. Grades were coded as slight (grade 1), moderate (grade 2), severe (grade 3) and very severe (grade 4). For certain signs, only its presence (grade 1) or absence (grade 0) was scored.  Animals were weighed individually on Day 1 (predose), 8 and 15. A fasted weight was recorded on the day of dosing. Terminal body weights were collected from animals found dead or euthanized moribund after Day 1. One animal was found dead on Day 2, no further mortality occurred. Hunched posture, uncoordinated movements and/or piloerection were noted on Day 1 for the animals. In addition, lethargy was noted for the animal that was found dead. No test item-related macroscopic abnormalities were noted in the gross necropsy post mortem examination of the animals. Based on the results of the study, the acute oral LD50 value of the test article is greater than 2,000 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

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:
2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
2009
Deviations:
no
GLP compliance:
yes
Test type:
traditional method
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 3M Company, Lot 1
- Expiration date of the lot/batch: 05 June, 2019
- Purity test date: 05 June, 2017

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Kept in a controlled temperature area set to maintain 18-24 C
- Stability under test conditions: Stable
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Raleigh
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: 11-12 weeks
- Weight at study initiation: 372-401 grams
- Fasting period before study: None
- Housing: All animals will be individually housed following receipt in suspended wire-mesh cages in an environmentally controlled room. Animals will be housed in clean cages elevated above cage board or other suitable material that will be changed at least three times each week. The cages will be cleaned and changed routinely at a frequency consistent with maintaining good animal health. All animals will be maintained in accordance with the Guide for the Care and Use of Laboratory Animals. The facilities at Charles River Ashland are fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC International). Due to the need for cage pan observations (fecal and/or urinary) in an acute study, animals will be single-housed in wire-mesh caging.
- Diet (e.g. ad libitum): PMI Nutrition International, LLC Certified Rodent LabDiet 5002 (block) will be offered ad libitum during the study, except during acclimation to restraint and the exposure period. Each lot utilized will be identified and recorded. SOPs provide specifications for acceptable levels of
heavy metals and pesticides that are reasonably expected to be present in the diet without interfering with the purpose or conduct of the study. No contaminants are reasonably expected to be present that would interfere with the objectives of the study; therefore, no testing will be conducted as part of the study.
- Water (e.g. ad libitum): Reverse osmosis-treated water will be available ad libitum, except during acclimation to restraint and the exposure period. Filters servicing the automatic watering system will be changed regularly according to SOPs. The municipal water supplying the laboratory will be analyzed for contaminants according to SOPs. No contaminants are reasonably expected to be present that would interfere with the objectives of the study, therefore, no testing will be conducted as part of the study.
- Acclimation period: At least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.1-23.0
- Humidity (%): 40.3-53.3
- Air changes (per hr): At least 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 03 November, 2017 To: 04 December, 2017
Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose only
Vehicle:
clean air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Exposures were conducted using a 0.74-L directed-flow (flow-past) nose-only exposure system (CH Technologies; Westwood, NJ). Animals were restrained in nose-only exposure holding tubes during exposure. Airflow rates through the system were set to provide the airflow required for generation and the dilution airflow, and to provide sufficient volumes for the number of animals to be exposed and for exposure atmosphere sampling.
- Exposure chamber volume: 0.74 L
- Method of holding animals in test chamber: Animals were restrained in nose-only exposure holding tubes during exposure.
- Source and rate of air: Airflow rates through the system were set to provide the airflow required for generation and the dilution airflow, and to provide sufficient volumes for the number of animals to be exposed and for exposure atmosphere sampling. Airflow to the exposure system was provided using a dry, breathing quality, in-house, compressed air source.
- Method of conditioning air: Humidified air was delivered to the nose-only exposure system using a Coilhose regulator (Model No. 8802K) and was controlled using a Linde rotameter-type flowmeter (Model No. FM4349, Union Carbide Corp.; Danbury, CT). To produce humidified air, dry compressed air passed through a muffler-type bubbler submerged in a 2-L Erlenmeyer flask filled with deionized water.
- Treatment of exhaust air: The exhaust atmosphere passed through the facility exhaust system,which consists of redundant exhaust blowers preceded by activated-charcoal and HEPA-filtration units.
- Temperature, humidity, pressure in air chamber: 22-23 C, 46-66 % humidity.

TEST ATMOSPHERE
- Brief description of analytical method used: Exposure atmosphere were sampled and analyzed at approximately every 5 to 30 minute using a gas chromatograph (GC). Samples of the exposure atmosphere were collected from the approximate animal-breathing zone of the nose-only exposure system and directed toward an external multi-position valve (Model E16, Valco Instruments Co., Inc.; Houston, TX) and a Hewlett Packard Model 3396 Series II integrator. Gas sampling injection onto the chromatography column occurred via an internal gas-sampling valve with a sample loop.
The chromatograph was displayed and the area under the sample peak was calculated and stored. The concentration in parts per million (ppm) was calculated using a ln-quadratic formula based on the GC calibration curve.
- Samples taken from breathing zone: yes
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
ca. 4 h
Concentrations:
148 mg/L (13,956 ppm), 213 mg/L (20,086 ppm)
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: Each animal was observed for mortality at the approximate midpoint of exposure and twice daily thereafter for 14 days (once in the morning and once in the afternoon, except on the day of scheduled necropsy). All animals in the 13,956 ppm group were observed once during the exposure, where only clinical signs visible in nose-only exposure restraint tubes were recorded. Each animal in the 13,956 and 20,086 ppm groups was observed following exposure upon unload from the nose-only tubes on Study Day 0, once 1-2 hours post-exposure, and once daily thereafter for 14 days for clinical signs of toxicity. Observations were recorded each day and included, but were not limited to: changes in the skin and fur, eyes and mucous membranes and also changes to the respiratory, circulatory, autonomic and central nervous systems, somatomotor activity, and behavior pattern. Body weights were obtained prior to exposure on Study Day 0 and on Post-Exposure Days 1, 3, 7, and 14. A final body weight was collected for all animals that died on study. Animals at the scheduled necropsy were euthanized by isoflurane anesthesia followed by exsanguination and subject to necropsy. The major organ systems of the cranial, thoracic, and abdominal cavities were examined for all animals. No tissue or organs were retained and the carcasses were discarded after necropsy.
- Necropsy of survivors performed: Yes
- Other examinations performed: clinical signs, body weights, gross necropsy
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 148 - < 213 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
The overall mortality incidence for the 213 mg/L (20,086 ppm) exposure was 8/10, with 3 male and all 5 female rats found dead by/on Study Day 2. All rats exposed to 148 mg/L (13,956 ppm) of the test article survived the 4-hour exposure and the subsequent 14-day observation period.
Clinical signs:
213 mg/L: Rats exposed to 213 mg/L test article demonstrated labored and shallow respiration, decreased respiration rates, dried red material in the facial area, unkempt appearance, red material around the mouth, nose, eye, trunk and forelimb, and yellow material on the trunk, rump, urogenital area, and anogenital area.

148 mg/L: Clinical observations of toxicity following the 148 mg/L (13,956 ppm) exposure included sporadic reports of increased respiration rate and dried red facial area for up to 2 days following the exposure.
Body weight:
213 mg/L: On Study Day 1, surviving males lost 46 to 52 g and surviving females lost 34 to 40 g in body weight. On Study Day 3, one surviving male lost 1 g and the second gained 4 g, with these 2 surviving males demonstrating weight gains over the remainder of the observation period.

148 mg/L: On Study Day 1, male rats lost 4 to 24 g and females lost 1 to 21 g of body weight. All exposed animals demonstrated body weight gains from Study Day 3 and for the remainder of the observation period.
Gross pathology:
213 mg/L: Gross necropsy of the 8 animals found dead revealed red fluid contents in the thoracic cavity (4/8), dark red discoloration of the lungs (4/8), white areas on the lungs (3/8) and/or white areas on the prostate (1/8). The 2 rats that survived the 213 mg/L (20,086 ppm) exposure to the end of the observation period demonstrated no macroscopic findings at the scheduled necropsy.

148 mg/L: No findings were noted upon gross necropsy of the animals exposed to 148 mg/L (13,956 ppm) at the scheduled necropsy.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, the 4-hour LC50 for the test article is greater than 148 mg/L (13, 956 ppm) but less than 213 mg/L (20, 086 ppm).
Executive summary:

The acute inhalation lethality potential of the test article was evaluated in male and female Sprague Dawley rats.  The study was conducted according to OECD 403 (2009) in compliance with OECD GLP. Rats (5/sex/dose) received nose-only exposure to 148 mg/L (13,956 ppm) or 213 mg/L (20,086 ppm) test article (vapor) for 4 hours followed by a 14-day observation period. Rats exposed to 213 mg/L (20,086 ppm) test article demonstrated labored and shallow respiration, decreased respiration rates, dried red material in the facial area, unkempt appearance, red material around the mouth, nose, eye, trunk and forelimb, and yellow material on the trunk, rump, urogenital area, and anogenital area. The overall mortality incidence for the 213 mg/L (20,086 ppm) exposure was 8/10, with 3 male and all 5 female rats found dead by/on Study Day 2. Gross necropsy of the 8 animals found dead revealed red fluid contents in the thoracic cavity (4/8), dark red discoloration of the lungs (4/8), white areas on the lungs (3/8) and/or white areas on the prostate (1/8). The 2 rats that survived the 20,086 ppm exposure to the end of the observation period demonstrated no macroscopic findings at the scheduled necropsy. All rats exposed to 148 mg/L (13,956 ppm) test article survived the 4-hour exposure and the subsequent 14-day observation period. Clinical observations of toxicity following the 148 mg/L (13,956 ppm) exposure included sporadic reports of increased respiration rate and dried red facial area for up to 2 days following the exposure. No findings were noted upon gross necropsy of the animals exposed to 148 mg/L (13,956 ppm) at the scheduled necropsy.  Under the conditions of this study, the 4-hour LC50 for the test article is greater than 148 mg/L (13,956 ppm) but less than 213 mg/L (20,086 ppm).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

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:
2017
Reliability:
1 (reliable without restriction)
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987
Deviations:
no
Remarks:
No deviations occurred that impacted the integrity of the study.
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 3M Company, Lot 1
- Expiration date of the lot/batch: 05 June, 2019
- Purity test date: 05 June, 2017

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature.
- Stability under test conditions: Stable

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: None, dosed neat.
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: Approximately 10 weeks old.
- Weight at study initiation: Males: 274 to 293 g, Females: 192-202 g
- Fasting period before study: None
- Housing: On arrival, animals were group housed (up to 5 animals of the same sex together) in polycarbonate cages (Makrolon MIV type; height 18 cm.) and following assignment to the study, animals were individually housed in polycarbonate cages (Makrolon MIII type; height 18 cm.) containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) equipped with water bottles. These housing conditions were maintained unless deemed inappropriate by the Study Director and/or Clinical Veterinarian. The room(s) in which the animals were kept were documented in the study records. Animals were separated during designated procedures/activities. Each cage was clearly labeled.
- Diet (e.g. ad libitum): Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany) was provided ad libitum throughout the study, except during designated procedures. The feed was analyzed by the supplier for nutritional components and environmental contaminants. Results of the analysis were provided by the supplier and are on file at the Test Facility. It is considered that there were no known contaminants in the feed that would interfere with the objectives of the study.
- Water (e.g. ad libitum): Municipal tap-water was freely available to each animal via water bottles. Periodic analysis of the water was performed, and results of these analyses are on file at the Test Facility. It is considered that there were no known contaminants in the water that would interfere with the objectives of the study.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24 C
- Humidity (%): 40-70
- Air changes (per hr): At least 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 17 October, 2017 To: 31 October, 2017
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Back
- % coverage: 5 x 7 cm area
- Type of wrap if used: The test item was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with aluminum foil and Coban elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, with water
- Time after start of exposure: 24 hours.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg body weight.

VEHICLE: None, dosed neat.
Duration of exposure:
24 hours
Doses:
2,000 mg/kg body weight.
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: Throughout the study, animals were observed for general health/mortality and moribundity twice daily, in the morning and at the end of the working day. Animals were not removed from cage during observation, unless necessary for identification or confirmation of possible findings. Postdose observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter. The observation period was 14 days. All the animals were examined for reaction to dosing. The onset, intensity and duration of these signs was recorded (if appropriate), particular attention being paid to the animals during and for the first hour after dosing. Animals were weighed individually on Day 1 (predose), 8 and 15.
- Necropsy of survivors performed: Yes
- Other examinations performed: clinical signs, body weight, macroscopic examination upon necropsy.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Chromodacryorrhoea of the snout was noted for one female on Day 2 only. No further clinical signs were noted for the animals.
Body weight:
The mean body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results of the study, the acute dermal LD50 of the test article is greater than 2,000 mg/kg body weight.
Executive summary:

The acute dermal lethality potential of the test article was evaluated in Wistar rats. The study was conducted according to OECD 402 (1987) in compliance with OECD GLP regulations. Rats (5/sex) received a single dermal application of 2,000 mg/kg body weight of the test article for 24 hours. The test item was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with aluminum foil and Coban elastic bandage. Throughout the study, animals were observed for general health/mortality and moribundity twice daily, in the morning and at the end of the working day. Animals were not removed from cage during observation, unless necessary for identification or confirmation of possible findings.  Postdose observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter. The observation period was 14 days. All the animals were examined for reaction to dosing. The onset, intensity and duration of these signs was recorded (if appropriate), particular attention being paid to the animals during and for the first hour after dosing.  Animals were weighed individually on Day 1 (predose), 8 and 15. No mortality occurred. Chromodacryorrhoea of the snout was noted for one female on Day 2 only. No further clinical signs were noted for the animals. The mean body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain. No abnormalities were found at macroscopic post mortem examination of the animals. Based on the results of the study, the acute dermal LD50 of the test article is greater than 2,000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Justification for classification or non-classification

The results do not meet the criteria for classification.