diff --git a/lib/galaxy/datatypes/converters/fastq_to_fqtoc.py b/lib/galaxy/datatypes/converters/fastq_to_fqtoc.py
index dfc4d4ffa66..cb0fb34b0e9 100644
--- a/lib/galaxy/datatypes/converters/fastq_to_fqtoc.py
+++ b/lib/galaxy/datatypes/converters/fastq_to_fqtoc.py
@@ -29,14 +29,12 @@ def main():
     with open(input_fname) as in_file, open(sys.argv[2], 'w') as out_file:
         out_file.write('{"sections" : [')
 
-        line = in_file.readline()
-        while line:
+        for _ in iter(in_file.readline, ''):
             current_line += 1
             if 0 == current_line % lines_per_chunk:
                 chunk_end = in_file.tell()
                 out_file.write(f'{{"start":"{chunk_begin}","end":"{chunk_end}","sequences":"{sequences}"}},')
                 chunk_begin = chunk_end
-            line = in_file.readline()
 
         chunk_end = in_file.tell()
         out_file.write(f'{{"start":"{chunk_begin}","end":"{chunk_end}","sequences":"{current_line % lines_per_chunk / 4}"}}')
diff --git a/lib/galaxy/datatypes/sequence.py b/lib/galaxy/datatypes/sequence.py
index 0a410c01b70..875c7c5730e 100644
--- a/lib/galaxy/datatypes/sequence.py
+++ b/lib/galaxy/datatypes/sequence.py
@@ -431,7 +431,7 @@ class Fasta(Sequence):
                 part_file = open(part_path, 'w')
                 log.debug(f"Writing {input_file} part to {part_path}")
                 start_offset = 0
-                for line in f:
+                for line in iter(f.readline, ''):
                     offset = f.tell()
                     if not line:
                         break
diff --git a/lib/galaxy/datatypes/sniff.py b/lib/galaxy/datatypes/sniff.py
index 7f5bee07975..40341e0bc6b 100644
--- a/lib/galaxy/datatypes/sniff.py
+++ b/lib/galaxy/datatypes/sniff.py
@@ -564,7 +564,7 @@ class FilePrefix:
     def line_iterator(self):
         s = self.string_io()
         s_len = len(s.getvalue())
-        for line in s:
+        for line in iter(s.readline, ''):
             if line.endswith("\n") or line.endswith("\r"):
                 yield line
             elif s.tell() == s_len and not self.truncated:
diff --git a/lib/galaxy/datatypes/tabular.py b/lib/galaxy/datatypes/tabular.py
index d7f6f070abe..cd3493c77ac 100644
--- a/lib/galaxy/datatypes/tabular.py
+++ b/lib/galaxy/datatypes/tabular.py
@@ -35,6 +35,8 @@ from . import dataproviders
 
 log = logging.getLogger(__name__)
 
+MAX_DATA_LINES = 100000
+
 
 @dataproviders.decorators.has_dataproviders
 class TabularData(data.Text):
@@ -270,7 +272,7 @@ class Tabular(TabularData):
     def get_column_names(self, first_line=None):
         return None
 
-    def set_meta(self, dataset, overwrite=True, skip=None, max_data_lines=100000, max_guess_type_data_lines=None, **kwd):
+    def set_meta(self, dataset, overwrite=True, skip=None, max_data_lines=MAX_DATA_LINES, max_guess_type_data_lines=None, **kwd):
         """
         Tries to determine the number of columns as well as those columns that
         contain numerical values in the dataset.  A skip parameter is used
@@ -367,7 +369,7 @@ class Tabular(TabularData):
             # NOTE: if skip > num_check_lines, we won't detect any metadata, and will use default
             with compression_utils.get_fileobj(dataset.file_name) as dataset_fh:
                 i = 0
-                for line in dataset_fh:
+                for line in iter(dataset_fh.readline, ''):
                     line = line.rstrip('\r\n')
                     if i == 0:
                         column_names = self.get_column_names(first_line=line)
diff --git a/test/unit/data/datatypes/test_tabular.py b/test/unit/data/datatypes/test_tabular.py
new file mode 100644
index 00000000000..3875e94f674
--- /dev/null
+++ b/test/unit/data/datatypes/test_tabular.py
@@ -0,0 +1,17 @@
+import tempfile
+
+from galaxy.datatypes.tabular import (
+    MAX_DATA_LINES,
+    Tabular,
+)
+from .util import MockDataset
+
+
+def test_tabular_set_meta_large_file():
+    with tempfile.NamedTemporaryFile(mode='w') as test_file:
+        for _ in range(MAX_DATA_LINES + 1):
+            test_file.write("A\tB\n")
+        test_file.flush()
+        dataset = MockDataset(id=1)
+        dataset.file_name = test_file.name
+        Tabular().set_meta(dataset)
diff --git a/test/unit/data/datatypes/util.py b/test/unit/data/datatypes/util.py
index 571264f2f10..d5d8b86a84a 100644
--- a/test/unit/data/datatypes/util.py
+++ b/test/unit/data/datatypes/util.py
@@ -18,10 +18,14 @@ class MockDataset:
     def __init__(self, id):
         self.id = id
         self.metadata = MockMetadata()
+        self.dataset = None
 
     def has_data(self):
         return True
 
+    def get_size(self):
+        return self.dataset and os.path.getsize(self.dataset.file_name)
+
 
 @contextmanager
 def get_dataset(filename, index_attr='bam_index', dataset_id=1, has_data=True):